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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
ALK wild-type	neuroblastoma	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) did not inhibit growth of ALK wild-type neuroblastoma cells in culture (PMID: 26554404).	26554404
ALK wild-type	endometrial cancer	no benefit	Dalantercept	Phase II	Actionable	In a Phase II clinical trial, treatment with Dalantercept (ACE-041) did not demonstrate activity as single agent in recurrent or persistent endometrial cancer, with a median progression-free survival (PFS) of 2.1 months, overall survival of 14.5 months, no objective responses, and stable disease in 57% (16/28) of patients (PMID: 25888978).	25888978
ALK wild-type	neuroblastoma	resistant	CEP-28122	Preclinical - Cell culture	Actionable	In a preclinical study, CEP-28122 did not inhibit growth of ALK wild-type neuroblastoma cells in culture (PMID: 22203728).	22203728
ALK wild-type	breast cancer	predicted - sensitive	Cisplatin + Dalantercept	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Dalantercept (ACE-041) in combination with Platinol (cisplatin) resulted in decreased tumor growth in cell line xenograft models of breast cancer (PMID: 26373572).	26373572
ALK wild-type	head and neck cancer	predicted - sensitive	Cisplatin + Dalantercept	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the addition of Dalantercept (ACE-041) to Platinol (cisplatin) treatment resulted in increased cytoxicity and decreased tumor growth in cell line xenograft models of head and neck cancer (PMID: 26373572).	26373572
ALK wild-type	melanoma	sensitive	Dalantercept + Doxorubicin	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Dalantercept (ACE-041) in combination with Adria (doxorubicin) resulted in decreased tumor growth in cell line xenograft models of melanoma, with increased efficacy over either agent alone (PMID: 26373572).	26373572
ALK wild-type	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Augtyro (repotrectinib) inhibited cell proliferation in transformed cell lines over expressing wild-type ALK in culture and suppressed tumor growth in xenograft models (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132).	detail...
ALK wild-type TP53 C176F	neuroblastoma	no benefit	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 C176F in culture (PMID: 26438783).	26438783
ALK wild-type TP53 H168R	neuroblastoma	no benefit	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Xalkori (crizotinib) did not improve the effect of Topotecan and Cytoxan (cyclophosphamide) on tumor growth suppression in xenograft models of a human neuroblastoma cell line harboring wild-type ALK and TP53 H168R (PMID: 26438783).	26438783
ALK wild-type TP53 P177T	neuroblastoma	no benefit	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 P177T in culture (PMID: 26438783).	26438783
ALK wild-type TP53 mut	neuroblastoma	no benefit	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 mutations in culture (PMID: 26438783).	26438783
ALK wild-type TP53 wild-type	neuroblastoma	no benefit	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and wild-type TP53 in culture (PMID: 26438783).	26438783
ALK L1196M	neuroblastoma	predicted - sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment resulted in a partial response with a progression-free survival over 544 days in a pediatric patient with neuroblastoma harboring ALK L1196M (PMID: 34780709; NCT01742286).	34780709
ALK L1196M	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) inhibited cell proliferation in transformed cell lines over expressing ALK L1196M in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132).	detail...
ALK L1196M	Advanced Solid Tumor	predicted - sensitive	Conteltinib	Preclinical - Biochemical	Actionable	In a preclinical study, Conteltinib (CT-707) inhibited ALK L1196M activity in an in vitro assay (PMID: 36424628).	36424628
ALK L1196M	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK L1196M in an in vitro assay (PMID: 34158340).	34158340
ALK L1196M	Advanced Solid Tumor	predicted - sensitive	APG-2449	Preclinical - Biochemical	Actionable	In a preclinical study, APG-2449 inhibited the kinase activity of ALK L1196M in culture (PMID: 35820889).	35820889
EML4 - ALK ALK L1196M	lung non-small cell carcinoma	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of non-small cell lung cancer cells expressing ALK L1196M in the context of EML4-ALK in culture (PMID: 21502504).	21502504
EML4 - ALK ALK L1196M	large cell neuroendocrine carcinoma	no benefit	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, a heavily pretreated patient with metastatic large cell neuroendocrine lung carcinoma harboring EML4-ALK (e20:e20) and ALK L1196M did respond to Alunbrig (brigatinib) treatment (PMID: 36207130).	36207130
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1196M in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853).	27780853
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	Advanced Solid Tumor	resistant	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated moderate resistance to ASP3026 in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing an EML4-ALK fusion and ALK L1196M in culture and in cell line xenograft models (PMID: 21575866).	21575866
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 24887559).	24887559
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated decreased sensitivity to Alecensa (alectinib) compared to cells expressing EML4-ALK with wild-type ALK, in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated resistance to Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196M was identified at progression on Xalkori (crizotinib) in a patient with non-small cell lung cancer harboring EML4-ALK (PMID: 34058070).	34058070
EML4 - ALK ALK L1196M	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, EML4-ALK and ALK L1196M were identified as acquired mutations in the pleural effusion from a patient with lung adenocarcinoma after his disease progressed on Xalkori (crizotinib) treatment (PMID: 28434515).	28434515
EML4 - ALK ALK L1196M	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, a cell line xenograft model expressing EML4-ALK with ALK L1196M was resistant to Xalkori (crizotinib) (PMID: 35820889).	35820889
EML4 - ALK ALK L1196M	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M in the context of EML4-ALK were insensitive to Xalkori (crizotinib) as demonstrated by a lack of growth inhibition and Alk phosphorylation in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784).	22277784
EML4 - ALK ALK L1196M	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1196M	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	lung non-small cell carcinoma	sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment resulted in 1 partial response and 1 patient with stable disease among 2 patients with non-small cell lung cancer harboring EML4-ALK (e13:e20) and ALK L1196M (PMID: 34890832; NCT01283516).	34890832
EML4 - ALK ALK L1196M	lung non-small cell carcinoma	sensitive	Ceritinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited cell survival and PI3K/AKT, MEK/ERK, and mTOR signaling in two human non-small cell lung carcinoma cell lines harboring the Xalkori (crizotinib) resistance mutation EML4-ALK ALK L1196M in culture and inhibited tumor growth in xenograft models of one of those cell lines (PMID: 24675041).	24675041
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK L1196M demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 26698910)	26698910
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited tumor growth in a cell line xenograft model expressing EML4-ALK with ALK L1196M (PMID: 35820889).	35820889
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	lung non-small cell carcinoma	sensitive	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and proliferation of non-small cell lung carcinoma cells over expressing ALK L1196M in the context of EML4-ALK in culture, and resulted in tumor regression in cell line xenograft models (PMID: 26144315).	26144315
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated resistance to Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated sensitivity to Lorbrena (lorlatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to growth inhibition mediated by Lorbrena (lorlatinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M	lung non-small cell carcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a clinical case study, Ensartinib (X-396) treatment resulted in a partial response in a non-small cell lung cancer patient harboring EML4-ALK (v5) with ALK L1196M and stable disease in another patient harboring EML4-ALK (v2) with ALK L1196M (PMID: 31446141).	31446141
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	Ensartinib	Preclinical	Actionable	In a preclinical study, Ensartinib (X-396) inhibited growth and Alk phosphorylation in cells expressing the Xalkori (crizotinib) resistance mutation, EML4-ALK ALK L1196M (PMID: 21613408).	21613408
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	Advanced Solid Tumor	conflicting	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were sensitive to Rozlytrek (entrectinib), resulting in anti-proliferative activity in culture (PMID: 26939704).	26939704
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) inhibited Alk activity and proliferation of transformed cells over expressing ALK L1196M in the context of EML4-ALK in culture (European Journal of Cancer , Volume 69, S32).	detail...
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) inhibited growth of transformed cells expressing ALK L1196M in the context of EML4-ALK in culture (PMID: 35421578).	35421578
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1196M in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M	lung non-small cell carcinoma	sensitive	NVL-655	Preclinical - Patient cell culture	Actionable	In a preclinical study, NVL-655 inhibited Alk signaling and growth in a patient-derived non-small cell lung cancer cell line harboring EML4-ALK and ALK L1196M in culture (PMID: 39269178).	39269178
EML4 - ALK ALK L1196M	Advanced Solid Tumor	predicted - sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 moderately inhibited viability of cells expressing EML4-ALK and ALK L1196M in culture (PMID: 39269178).	39269178
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	XMU-MP-5	Preclinical - Cell line xenograft	Actionable	In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34845836).	34845836
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	APG-2449	Preclinical - Cell line xenograft	Actionable	In a preclinical study, APG-2449 inhibited tumor growth in a cell line xenograft model expressing EML4-ALK with ALK L1196M (PMID: 35820889).	35820889
EML4 - ALK ALK L1196M	Advanced Solid Tumor	sensitive	TQ-B3139	Preclinical - Cell line xenograft	Actionable	In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of cells expressing EML4-ALK with ALK L1196M in culture and inhibited tumor growth in a cell line xenograft model (PMID: 30210922).	30210922
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, introduction of an additional ALK mutation L1198F in transformed cells expressing ALK L1196M in the context of EML4-ALK reduced resistance to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	Ceritinib	Preclinical	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1196M ALK L1198F	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK G1269A	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196M and G1269A were identified in post-progression lymph node biopsy with a poorly differentiated adenocarcinoma pathology in a patient with metastatic lung adenocarcinoma and transformed small cell carcinoma harboring EML4-ALK, who previously achieved a partial response on Alecensa (alectinib) treatment (PMID: 38961982).	38961982
EML4 - ALK ALK L1196M ALK G1269A	lung non-small cell carcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical study, a patient with non-small cell lung cancer harboring EML4-ALK demonstrated a partial response when treated with Xalkori (crizotinib), however, after 6 months the patient progressed and was found to harbor two secondary resistance mutations, ALK G1269A and ALK L1196M (PMID: 23344087).	23344087
EML4 - ALK ALK L1196M ALK G1269A	lung adenocarcinoma	predicted - sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, fifth-line Zykadia (ceritinib) treatment resulted in a partial response with a progression-free survival of approximately 5 months in a patient with metastatic poorly differentiated lung adenocarcinoma harboring EML4-ALK, ALK G1269A, and ALK L1196M (PMID: 38961982).	38961982
EML4 - ALK ALK L1196M ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK C1156Y ALK L1196M	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK treated on a clinical trial achieved a partial response when treated with Xalkori (crizotinib), however, after 5 months, the patient progressed and was found to harbor secondary resistance mutations, ALK C1156Y and ALK L1196M (PMID: 20979473; NCT00585195).	20979473
EML4 - ALK ALK C1156Y ALK L1196M	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
ALK rearrange ALK L1196M	lung non-small cell carcinoma	predicted - resistant	Brigatinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK L1196M was identified in 17% (12/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK L1196M	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, ALK L1196M was identified in one patient with non-small cell lung cancer harboring an ALK rearrangement after progression on first-line Alecensa (alectinib) and in 27% (15/56) of patients after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554).	detail...
ALK rearrange ALK L1196M	lung non-small cell carcinoma	predicted - resistant	Alectinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK L1196M was identified in 22% (10/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542).	31358542
ALK rearrange ALK L1196M	lung non-small cell carcinoma	resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196M was identified in biopsies from a non-small cell lung cancer patient harboring an ALK rearrangement who developed resistance to Xalkori (crizotinib) (PMID: 22277784).	22277784
ALK rearrange ALK L1196M	lung non-small cell carcinoma	resistant	Crizotinib	Case Reports/Case Series	Actionable	In a retrospective analysis, four non-small cell lung cancer patients harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and were found to have acquired ALK L1196M (PMID: 25724526).	25724526
ALK rearrange ALK L1196M	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in disease progression after 4 months of therapy in a patient with ALK rearranged lung adenocarcinoma, ALK L1196M was detected in the biopsies at disease progression (PMID: 31585938).	31585938
ALK rearrange ALK L1196M	lung non-small cell carcinoma	predicted - resistant	Ceritinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK L1196M was identified in 17% (12/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK L1196M	lung non-small cell carcinoma	sensitive	Lorlatinib	Clinical Study	Actionable	In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK L1196M (n=12), with an objective response rate of 67% (8/12; 95% CI 35.0-90.0), a median duration of response not reached (NR) (95% CI 5.2-NR), and a median progression-free survival not reached (95% CI 2.8-NR) (PMID: 30892989; NCT01970865).	30892989
ALK rearrange ALK L1196M	lung non-small cell carcinoma	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in guidelines as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK L1196M (NCCN.org).	detail...
ALK rearrange ALK L1196M	lung non-small cell carcinoma	predicted - resistant	Ensartinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK L1196M was identified in 17% (12/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
EML4 - ALK ALK I1171S ALK L1196M	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK I1171S was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK F1174C ALK L1196M	lung adenocarcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196M was identified in the post-progression biopsy of a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20) and ALK F1174C, who previously responded to Lorbrena (lorlatinib) treatment (PMID: 36093526).	36093526
EML4 - ALK ALK F1174C ALK L1196M	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK F1174L ALK L1196M	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK F1174L was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK F1174V ALK L1196M	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK I1179V ALK L1196M	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK I1179V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK L1196M ALK L1256F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK L1196M ALK G1202R	lung non-small cell carcinoma	resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196M and ALK G1202R were identified in the post-progression circulating tumor DNA of a patient with non-small cell lung cancer harboring EML4-ALK who progressed on treatment with Alunbrig (brigatinib), and in a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Alunbrig (brigatinib) in culture (PMID: 38448512, PMID: 36806896).	36806896 38448512
EML4 - ALK ALK L1196M ALK G1202R	lung non-small cell carcinoma	resistant	Brigatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK, ALK G1202R, and ALK L1196M was resistant to Alunbrig (brigatinib) treatment in culture (PMID: 39269178).	39269178
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	lung non-small cell carcinoma	resistant	Alectinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK, ALK G1202R, and ALK L1196M was resistant to Alecensa (alectinib) treatment in culture (PMID: 39269178).	39269178
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Alecensa (alectinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK L1196M compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1196M were resistant to Alecensa (alectinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and L1196M were resistant to Alecensa (alectinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	lung non-small cell carcinoma	resistant	Crizotinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK, ALK G1202R, and ALK L1196M was resistant to Xalkori (crizotinib) treatment in culture (PMID: 39269178).	39269178
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Xalkori (crizotinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK L1196M compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1196M were resistant to Xalkori (crizotinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and L1196M were resistant to Xalkori (crizotinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	lung non-small cell carcinoma	resistant	Ceritinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK, ALK G1202R, and ALK L1196M was resistant to Zykadia (ceritinib) treatment in culture (PMID: 39269178).	39269178
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Zykadia (ceritinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and L1196M compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	lung non-small cell carcinoma	resistant	Lorlatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK, ALK G1202R, and ALK L1196M was resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 39269178).	39269178
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1202R in the context of EML4-ALK that acquired resistance to Lorbrena (lorlatinib) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment did not inhibit proliferation of transformed cells expressing ALK G1202R and L1196M compound mutation in the context of EML4-ALK in culture and resulted in only 18% tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1196M were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and L1196M were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and L1196M were resistant to Xospata (gilteritinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell line xenograft	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1196M and ALK G1202R compound mutation in the context of EML4-ALK in culture, and resulted in complete tumor growth regression in a cell line xenograft model (PMID: 34158340).	34158340
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK G1202R and L1196M in culture (PMID: 36201110).	36201110
EML4 - ALK ALK L1196M ALK G1202R	lung non-small cell carcinoma	sensitive	NVL-655	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, NVL-655 inhibited Alk signaling and viability of a patient-derived non-small cell lung cancer cell line harboring EML4-ALK, ALK G1202R, and ALK L1196M in culture and induced tumor regression in a patient-derived xenograft (PDX) model and a cell line xenograft model (PMID: 39269178).	39269178
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	sensitive	NVL-655	Preclinical	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK, ALK G1202R, and ALK L1196M in culture and induced tumor regression in a transplant model and decreased brain tumor volume and increased survival in an intracranial transplant model (PMID: 39269178).	39269178
ALK rearrange ALK L1196M ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Brigatinib	Case Reports/Case Series	Actionable	In a Phase III trial (ALTA-1L), ALK L1196M and ALK G1202R were identified in the post-progression plasma ctDNA of a patient with ALK-positive non-small cell lung cancer who previously responded to treatment with Alunbrig (brigatinib) (PMID: 31668326).	31668326
ALK rearrange ALK L1196M ALK G1202R	lung non-small cell carcinoma	resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R and ALK L1196M developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 29650534).	29650534
ALK rearrange ALK L1196M ALK G1202R	lung non-small cell carcinoma	resistant	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is not indicated for use as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK L1196M and G1202R compound mutations (NCCN.org).	detail...
ALK rearrange ALK V1180L ALK L1196M ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1202R and ALK L1196M were identified at disease progression while on Alunbrig (brigatinib) treatment in liquid biopsy of a patient with ALK-positive non-small cell lung cancer also harboring an ALK V1180L (PMID: 29935304).	29935304
ALK L1196M ALK pos	lung non-small cell carcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 25% (1/12, all partial responses) and stable disease in 67% (8/12) of patients with ALK-positive non-small cell lung cancer harboring ALK L1196M (PMID: 31628085; NCT0321569).	31628085
ALK rearrange ALK L1196M ALK D1203N	lung adenocarcinoma	predicted - resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, Zykadia (ceritinib) treatment resulted in disease progression after 5 months of therapy in a patient with lung adenocarcinoma harboring ALK rearrangement and an acquired ALK L1196M, ALK D1203N was detected in the biopsies at disease progression (PMID: 31585938).	31585938
ALK rearrange ALK L1196M ALK D1203N	lung adenocarcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with lung adenocarcinoma harboring ALK rearrangement and acquired ALK L1196M, ALK D1203N mutations demonstrated primary resistance to Lorbrena (lorlatinib) treatment, resulted in immediate disease progression (PMID: 31585938).	31585938
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	predicted - resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK D1203N	lung non-small cell carcinoma	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK (e13:e20) with ALK L1196M and D1203N was resistant to Xalkori (crizotinib) in culture (PMID: 37748191).	37748191
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK D1203N	lung adenocarcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e19:e20) and ALK D1203N who responded to Lorbrena (lorlatinib) treatment was found to have acquired ALK L1196M upon disease progression (PMID: 38149055).	38149055
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1196M and ALK D1203N compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938).	31585938
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196M ALK D1203N	Advanced Solid Tumor	predicted - resistant	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1196M in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	malignant pleural mesothelioma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196M and ALK I1171N were identified in the post-progression biopsy of a patient with malignant pleural mesothelioma harboring EML4-ALK who previously responded to Alecensa (alectinib) treatment (PMID: 32600123).	32600123
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1196M in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	malignant pleural mesothelioma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in tumor regression and a partial response lasting 3.6 months in a patient with malignant pleural mesothelioma harboring EML4-ALK, ALK L1196M, and ALK I1171N (PMID: 32600123).	32600123
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1196M	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1196M in culture (PMID: 33627640).	33627640
EML4 - ALK ALK C1156Y ALK L1196M ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung cancer patient with EML4-ALK, ALK G1202R, ALK L1196M, and ALK V1180L prior to Lorbrena (lorlatinib) treatment demonstrated loss of the V1180L variant and acquisition of ALK C1156Y following progression on Lorbrena (lorlatinib) (PMID: 31358542).	31358542
ALK L1196M ALK L1198F	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK L1196M and ALK L1198F compound mutation in an in vitro assay (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N ALK L1196M ALK G1202R	malignant pleural mesothelioma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1202R was identified in the post-progression biopsy of a patient with malignant pleural mesothelioma harboring EML4-ALK with ALK L1196M and ALK I1171N who previously responded to Lorbrena (lorlatinib) treatment (PMID: 32600123).	32600123
ALK fusion ALK L1196M ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196M was identified as an acquired mutation in a non-small cell lung cancer patient harboring an ALK fusion with ALK G1202R who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063).	35726063
EML4 - ALK ALK L1196M ALK G1202R ALK D1203N	large cell neuroendocrine carcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196M, ALK D1203N, and ALK G1202R were identified on post-progression biopsy in a patient with metastatic large cell neuroendocrine lung carcinoma harboring EML4-ALK (e20:e20), who previously achieved disease stabilization for 8 months with Lorbrena (lorlatinib) treatment (PMID: 36207130).	36207130
EML4 - ALK ALK I1171T ALK F1174L ALK L1196M ALK D1203N ALK E1210K ALK G1269A	lung adenocarcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196M, D1203N, and I1171T were identified at the time of progression on Lorbrena (lorlatinib) treatment in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK G1269A, ALK F1174L, and ALK E1210K (PMID: 35123209).	35123209
ALK I1171T ALK R1192P ALK L1196M ALK F1245V	neuroblastoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, a neuroblastoma patient harboring ALK F1245V developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired additional ALK variants, I1171T, R1192P, and L1196M, via circulating tumor DNA (PMID: 37147298; NCT03107988).	37147298
ALK L1196M ALK R1275Q	neuroblastoma	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a neuroblastoma cell line harboring ALK R1275Q and expressing L1196M was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298).	37147298
ALK F1174L ALK L1196M	neuroblastoma	resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, two neuroblastoma patients harboring ALK F1174L developed progressive disease on treatment with Lorbrena (lorlatinib) and were found to have acquired ALK L1196M via circulating tumor DNA, and a neuroblastoma cell line harboring ALK F1174L and expressing L1196M was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298; NCT03107988).	37147298
EML4 - ALK ALK L1122V ALK L1196M ALK D1203N ALK G1269A	lung adenocarcinoma	predicted - resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK D1203N and L1122V were identified in post-progression biopsy in a patient with metastatic lung adenocarcinoma harboring EML4-ALK, ALK G1269A, and ALK L1196M, who previously achieved a partial response on Zykadia (ceritinib) treatment (PMID: 38961982).	38961982
ALK F1174L	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing ALK F1174L was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722).	27049722
ALK F1174L	neuroblastoma	conflicting	Crizotinib	Case Reports/Case Series	Actionable	In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, although all 3 patients harboring ALK F1174L had disease progression after only 1 cycle of treatment (PMID: 33568345; NCT00939770).	33568345
ALK F1174L	neuroblastoma	conflicting	Crizotinib	Case Reports/Case Series	Actionable	In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) therapy resulted in stable disease lasting 19 months in a patient with advanced neuroblastoma harboring ALK F1174L (PMID: 29352732; NCT00939770).	29352732
ALK F1174L	neuroblastoma	conflicting	Crizotinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1174L in culture, and only delayed tumor growth in patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404).	26554404
ALK F1174L	neuroblastoma	conflicting	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) treatment inhibited viability of neuroblastoma cell lines harboring ALK F1174L in culture (PMID: 38032104).	38032104
ALK F1174L	neuroblastoma	sensitive	Ceritinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited downstream signaling and viability in neuroblastoma cell lines harboring ALK F1174L in culture and reduced cell invasion in a cell line xenograft model (PMID: 38032104).	38032104
ALK F1174L	neuroblastoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response in 3 of 5 patients and a partial response in 1 of 5 patients with neuroblastoma harboring ALK F1174L (PMID: 37561984).	37561984
ALK F1174L	neuroblastoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response lasting 13 mo in a pediatric patient with metastatic, relapsed neuroblastoma harboring ALK F1174L and PIK3CA C692Ffs*8, who had previously progressed on combination therapy with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan (PMID: 34210658).	34210658
ALK F1174L	neuroblastoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response lasting 10 months in a pediatric patient with metastatic neuroblastoma harboring ALK F1174L, along with MYCN amplification (PMID: 39177282).	39177282
ALK F1174L	neuroblastoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in stable disease after 4 cycles in a pediatric patient with neuroblastoma harboring ALK F1174L (PMID: 36765519).	36765519
ALK F1174L	neuroblastoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a minor response with stable disease in a neuroblastoma patient harboring ALK F1174L (PMID: 37147298; NCT03107988).	37147298
ALK F1174L	neuroblastoma	predicted - sensitive	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited downstream signaling, viability, and invasion in neuroblastoma cell lines harboring ALK F1174L in culture, and decreased tumor growth and increased survival in cell line xenograft models (PMID: 38032104).	38032104
ALK F1174L	neuroblastoma	predicted - sensitive	Lorlatinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells over expressing ALK F1174L in culture, and induced rapid and sustained complete tumor regression in both patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404).	26554404
ALK F1174L	neuroblastoma	predicted - sensitive	Lorlatinib	Preclinical	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment induced tumor regression in a transgenic mouse model of neuroblastoma harboring ALK F1174L (PMID: 27483357).	27483357
ALK F1174L	neuroblastoma	predicted - sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, neuroblastoma cells harboring ALK F1174L were resistant to Lorbrena (lorlatinib) in culture (PMID: 30322862).	30322862
ALK F1174L	neuroblastoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in partial remission in a neuroblastoma patient harboring ALK F1174L (PMID: 38787533; NCT04477681).	38787533
ALK F1174L	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells overexpressing ALK F1174L in culture (PMID: 26554404).	26554404
ALK F1174L	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK F1174L in culture (PMID: 27483357).	27483357
ALK F1174L	neuroblastoma	sensitive	Vandetanib	Preclinical	Actionable	In a preclinical study, Caprelsa (vandetanib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK F1174L (corresponds to F1178L in mouse) and subsequent upregulation of Ret (PMID: 24811913).	24811913
ALK F1174L	neuroblastoma	predicted - sensitive	Entrectinib	Case Reports/Case Series	Actionable	In a Phase I/II trial, Rozlytrek (entrectinib) treatment resulted in a complete response in a patient with neuroblastoma harboring ALK F1174L (PMID: 35395680; NCT02650401).	35395680
ALK F1174L	neuroblastoma	sensitive	AZD3463	Preclinical - Cell line xenograft	Actionable	In a preclinical study, AZD3463 inhibited growth of neuroblastoma cells harboring ALK F1174L in culture, resulted in near complete tumor regression in cell line xenograft models (PMID: 26786851).	26786851
ALK F1174L	neuroblastoma	sensitive	CEP-28122	Preclinical - Cell culture	Actionable	In a preclinical study, CEP-28122 inhibited growth of neuroblastoma cells harboring ALK F1174L in culture (PMID: 22203728).	22203728
ALK F1174L	neuroblastoma	sensitive	Ceritinib + Ribociclib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of Zykadia (ceritinib) and Kisqali (ribociclib) synergistically inhibited proliferation and Alk phosphorylation and induced cell cycle arrest in neuroblastoma cell line harboring ALK F1174L in culture, and induced complete tumor regression and increased event-free survival compared to either agent alone (P<0.0001) in a cell line xenograft model (PMID: 27986745).	27986745
ALK F1174L	neuroblastoma	conflicting	Crizotinib + Cyclophosphamide + Topotecan	Case Reports/Case Series	Actionable	In a clinical case study, combination treatment with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan resulted in a complete response after 2 cycles in a one pediatric patient, and a clinical response with stable disease lasting 7 months in another pediatric patient with relapsed neuroblastoma harboring ALK F1174L (PMID: 36765519).	36765519
ALK F1174L	neuroblastoma	conflicting	Crizotinib + Cyclophosphamide + Topotecan	Case Reports/Case Series	Actionable	In a clinical case study, combination treatment with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan resulted in progressive disease within 1 cycle of therapy in a pediatric patient with metastatic, relapsed neuroblastoma harboring ALK F1174L and PIK3CA C692Ffs*8 (PMID: 34210658).	34210658
ALK F1174L	neuroblastoma	sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) inhibited proliferation of a neuroblastoma cell line harboring ALK F1174L in culture (PMID: 31852910).	31852910
ALK F1174L	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) decreased Alk phosphorylation and neurite outgrowth in cells expressing ALK F1174L in culture (PMID: 31852910).	31852910
ALK F1174L	neuroblastoma	sensitive	SHP099	Preclinical - Cell culture	Actionable	In a preclinical study, SHP099 decreased viability of neuroblastoma cell lines harboring ALK F1174L in culture (PMID: 38032104).	38032104
ALK F1174L	Advanced Solid Tumor	predicted - sensitive	Conteltinib	Preclinical - Biochemical	Actionable	In a preclinical study, Conteltinib (CT-707) inhibited ALK F1174L activity in an in vitro assay (PMID: 36424628).	36424628
ALK F1174L	neuroblastoma	sensitive	TNO155	Preclinical - Cell line xenograft	Actionable	In a preclinical study, TNO155 decreased viability and invasion of neuroblastoma cell lines harboring ALK F1174L in culture and decreased tumor growth and cell invasion and increased survival in cell line xenograft models (PMID: 38032104).	38032104
ALK F1174L	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1174L in an in vitro assay (PMID: 34158340).	34158340
ALK F1174L	neuroblastoma	sensitive	Crizotinib + SHP099	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of SHP099 and Xalkori (crizotinib) synergistically decreased viability of neuroblastoma cell lines harboring ALK F1174L in culture (PMID: 38032104).	38032104
ALK F1174L	neuroblastoma	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of neuroblastoma cell lines harboring ALK F1174L in culture (PMID: 39269178).	39269178
ALK F1174L	neuroblastoma	sensitive	TQ-B3139	Preclinical - Cell line xenograft	Actionable	In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of a neuroblastoma cell line harboring ALK F1174L in culture and inhibited tumor growth in a cell line xenograft model (PMID: 30210922).	30210922
ALK F1174L	neuroblastoma	sensitive	Cyclophosphamide + Doxorubicin + Lorlatinib + Vincristine Sulfate	Preclinical	Actionable	In a preclinical study, the combination of Lorbrena (lorlatinib), Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), and Oncovin (vincristine) resulted in an early tumor response, and improved survival in a genetically engineered mouse model of neuroblastoma harboring ALK F1174L (PMID: 36602782).	36602782
ALK F1174L	neuroblastoma	sensitive	4SC-205 + Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, the combination of 4SC-205 and Lorbrena (lorlatinib) inhibited viability to a greater degree than either therapy alone in neuroblastoma cell lines harboring ALK F1174L (PMID: 34709738).	34709738
ALK F1174L	neuroblastoma	sensitive	4SC-205 + Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, the combination of 4SC-205 and Zykadia (ceritinib) inhibited viability to a greater degree than either therapy alone in neuroblastoma cell lines harboring ALK F1174L (PMID: 34709738).	34709738
ALK F1174L	neuroblastoma	sensitive	CCC-003	Preclinical - Cell line xenograft	Actionable	In a preclinical study, CCC-003 treatment resulted in decreased cell proliferation and induction of apoptosis in neuroblastoma cell lines harboring ALK F1174L in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 34591871).	34591871
ALK F1174L	Advanced Solid Tumor	sensitive	CCC-003	Preclinical - Cell culture	Actionable	In a preclinical study, CCC-003 inhibited viability in transformed cells expressing ALK F1174L in culture (PMID: 34591871).	34591871
ALK F1174L	neuroblastoma	sensitive	Ceritinib + TNO155	Preclinical - Cell line xenograft	Actionable	In a preclinical study, treatment with the combination of TNO155 and Zykadia (ceritinib) resulted in enhanced inhibition of downstream signaling and invasion and synergistically decreased viability of neuroblastoma cell lines harboring ALK F1174L in culture and led to significantly decreased tumor growth in a cell line xenograft model compared to either agent alone (PMID: 38032104).	38032104
ALK F1174L	neuroblastoma	sensitive	Lorlatinib + TNO155	Preclinical - Cell line xenograft	Actionable	In a preclinical study, treatment with the combination of TNO155 and Lorbrena (lorlatinib) inhibited downstream signaling and invasion and synergistically decreased viability of neuroblastoma cell lines harboring ALK F1174L in culture, decreased growth and improved survival compared to either agent alone in cell line xenograft models, and treatment with TNO155 restored sensitivity to Lorbrena (lorlatinib) in Lorbrena (lorlatinib)-resistant cell lines and cell line xenograft models (PMID: 38032104).	38032104
ALK F1174L	neuroblastoma	sensitive	Crizotinib + TNO155	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of TNO155 and Xalkori (crizotinib) synergistically decreased viability of neuroblastoma cell lines harboring ALK F1174L in culture (PMID: 38032104).	38032104
ALK F1174L	neuroblastoma	sensitive	Ceritinib + SHP099	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of SHP099 and Zykadia (ceritinib) decreased invasion and synergistically decreased viability of neuroblastoma cell lines harboring ALK F1174L in culture (PMID: 38032104).	38032104
ALK F1174L	neuroblastoma	sensitive	Lorlatinib + SHP099	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of SHP099 and Lorbrena (lorlatinib) decreased invasion and synergistically decreased viability of neuroblastoma cell lines harboring ALK F1174L in culture (PMID: 38032104).	38032104
ALK F1174L TP53 wild-type	neuroblastoma	sensitive	Ceritinib + CGM097	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of Zykadia (ceritinib) and CGM097 inhibited Alk signaling and resulted in synergistic inhibition of proliferation in a TP53 wild-type neuroblastoma cell line harboring ALK F1174L in culture and induced tumor regression in a cell line xenograft model (PMID: 28425916).	28425916
ALK F1174L TP53 wild-type	neuroblastoma	sensitive	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in xenograft models of a crizotinib-resistant human neuroblastoma cell line harboring ALK F1174L and wild-type TP53 (PMID: 26438783).	26438783
ALK F1174L TP53 wild-type	neuroblastoma	sensitive	Idasanutlin + TAE684	Case Reports/Case Series	Actionable	In a preclinical study, TAE684 and Idasanutlin (RG7388) synergistically inhibited growth and induced apoptosis in a TP53 wild-type neuroblastoma cell line harboring ALK F1174L in culture (PMID: 36602782).	36602782
ALK F1174L TP53 wild-type	neuroblastoma	sensitive	Alectinib + Idasanutlin	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth and induced apoptosis in a TP53 wild-type neuroblastoma cell line harboring ALK F1174L in culture (PMID: 36602782).	36602782
EML4 - ALK ALK F1174L	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 35421578).	35421578
EML4 - ALK ALK F1174L	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were less sensitive to Alunbrig (brigatinib)-mediated growth inhibition compared to cells expressing EML4-ALK in culture (PMID: 27009859).	27009859
EML4 - ALK ALK F1174L	Advanced Solid Tumor	resistant	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK F1174L	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859).	27009859
EML4 - ALK ALK F1174L	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174L in culture and in xenograft models (PMID: 24887559).	24887559
EML4 - ALK ALK F1174L	Advanced Solid Tumor	conflicting	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK F1174L in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) in culture (PMID: 27780853).	27780853
EML4 - ALK ALK F1174L	Advanced Solid Tumor	conflicting	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859).	27009859
EML4 - ALK ALK F1174L	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were resistant to Zykadia (ceritinib)-mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK F1174L	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK F1174L in the context of EML4-ALK in culture (PMID: 26144315).	26144315
EML4 - ALK ALK F1174L	Advanced Solid Tumor	sensitive	AZD3463	Preclinical - Cell culture	Actionable	In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859).	27009859
EML4 - ALK ALK F1174L	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 35421578).	35421578
EML4 - ALK ALK F1174L	Advanced Solid Tumor	predicted - resistant	XMU-MP-5	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L did not demonstrate sensitivity to treatment with XMU-MP-5 in culture (PMID: 34845836).	34845836
EML4 - ALK ALK F1174L	Advanced Solid Tumor	sensitive	APG-2449	Preclinical - Cell culture	Actionable	In a preclinical study, APG-2449 inhibited proliferation of a cell line expressing EML4-ALK with ALK F1174L in culture (PMID: 35820889).	35820889
ALK F1174L ALK L1198P	neuroblastoma	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, expression of ALK L1198P in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to Xalkori (crizotinib) in culture (PMID: 21948233).	21948233
ALK F1174L ALK L1198P	neuroblastoma	resistant	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, expression of ALK L1198P in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233).	21948233
ALK G1123S ALK F1174L	neuroblastoma	resistant	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, expression of ALK G1123S in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233).	21948233
ALK G1123D ALK F1174L	neuroblastoma	resistant	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, expression of ALK G1123D in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233).	21948233
ALK F1174L ALK amp	neuroblastoma	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174L in culture (PMID: 29907598).	29907598
ALK F1174L ALK amp	neuroblastoma	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174L in culture (PMID: 29907598).	29907598
EML4 - ALK ALK F1174L ALK L1198V	lung non-small cell carcinoma	resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK progressed while being treated with Alunbrig (brigatinib) and was subsequently found to harbor two resistance mutations, ALK F1174L and ALK L1198V, which were both in cis (PMID: 29636358).	29636358
ALK rearrange ALK F1174L	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, ALK F1174L was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554).	detail...
ALK rearrange ALK F1174L	lung adenocarcinoma	predicted - resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK F1174L was identified in biopsies at disease progression after 4 months of Zykadia (ceritinib) treatment in a patient with lung adenocarcinoma harboring ALK rearrangement (PMID: 31585938).	31585938
ALK rearrange ALK F1174L	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK F1174C/L was identified in 14% (4/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542).	31358542
EML4 - ALK ALK F1174L ALK G1269A	lung adenocarcinoma	predicted - resistant	Belizatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK F1174L and ALK G1269A were identified as newly acquired mutations in the pleural effusion from a patient with lung adenocarcinoma harboring an acquired EML4-ALK after his disease progressed on Belizatinib (TSR-011) treatment (PMID: 28434515).	28434515
EML4 - ALK ALK F1174L ALK D1203N ALK G1269A	lung adenocarcinoma	predicted - resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK D1203N were identified as a newly acquired mutation in the pleural effusion from a patient with lung adenocarcinoma after his disease progressed on Zykadia (ceritinib) treatment, in addition to the EML4-ALK, ALK F1174L, and ALK G1269A acquired after disease progression on Xalkori (crizotinib) and Belizatinib (TSR-011) sequentially (PMID: 28434515).	28434515
ALK rearrange ALK F1174L ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588).	31439588
ALK F1174L ALK pos	lung non-small cell carcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 71% (5/7, all partial responses) of patients with ALK-positive non-small cell lung cancer harboring ALK F1174L (n=5) or ALK F1174V (n=1) (PMID: 31628085; NCT0321569).	31628085
EML4 - ALK ALK T1151M ALK C1156Y ALK F1174L ALK G1202R ALK S1206F ALK G1269A	lung adenocarcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 3.7 months therapy in a patient with lung adenocarcinoma harboring EML4-ALK and ALK G1202R, at disease progression, ALK F1174L in cis wth ALK G1202R was identified in biopsies, and ALK C1156Y, G1269A, S1206F, and T1151M were identified in ctDNA (PMID: 31585938).	31585938
EML4 - ALK ALK F1174L ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK F1174L and ALK G1202R compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938).	31585938
EML4 - ALK ALK F1174L ALK G1202R	Advanced Solid Tumor	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK, ALK G1202R, and ALK F1174L in culture (PMID: 39269178).	39269178
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174L	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640).	33627640
ALK F1174L ALK R1275Q	neuroblastoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, and a patient harboring both ALK F1174L and ALK R1275Q stayed on treatment for 3 cycles until disease progression (PMID: 33568345; NCT00939770).	33568345
EML4 - ALK ALK E1129V ALK I1171T ALK F1174C ALK F1174L ALK F1174V ALK G1269A	lung adenocarcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in stable disease with a progression-free survival of 10 months in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK E1129V, F1174C, F1174L, F1174V, I1171T, and G1269A (PMID: 36093526).	36093526
EML4 - ALK ALK E1129V ALK I1171T ALK F1174C ALK F1174L ALK F1174V ALK G1269A	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK E1129V, F1174C, F1174L, F1174V, I1171T, and G1269A were identified in the post-progression biopsy of a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e13:e20), who previously responded to Xalkori (crizotinib) treatment (PMID: 36093526).	36093526
EML4 - ALK ALK F1174L ALK S1189C	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK along with ALK F1174L in cis with ALK S1189C did not respond to first-line Xalkori (crizotinib) treatment (PMID: 36506539).	36506539
EML4 - ALK ALK F1174L ALK S1189C	lung adenocarcinoma	predicted - resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK along with ALK F1174L in cis with ALK S1189C did not respond to second-line Zykadia (ceritinib) treatment (PMID: 36506539).	36506539
EML4 - ALK ALK F1174L ALK E1210K ALK G1269A	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK G1269A, ALK F1174L, and ALK E1210K (PMID: 35123209).	35123209
ALK F1174L NRAS Q61K	neuroblastoma	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, expression of NRAS Q61K in a neuroblastoma cell line harboring ALK F1174L conferred resistance to Zykadia (ceritinib) in culture (PMID: 35689207).	35689207
ALK F1174L NRAS Q61K	neuroblastoma	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, expression of NRAS Q61K in a neuroblastoma cell line harboring ALK F1174L conferred resistance to Lorbrena (lorlatinib) in culture (PMID: 35689207).	35689207
ALK F1174L FGFR1 N546K	neuroblastoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, a neuroblastoma patient harboring ALK F1174L developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired FGFR1 N546K via circulating tumor DNA (PMID: 37147298; NCT03107988).	37147298
ALK F1174L PIK3CA H1047R	neuroblastoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, a neuroblastoma patient harboring ALK F1174L developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired PIK3CA H1047R via circulating tumor DNA (PMID: 37147298; NCT03107988).	37147298
ALK F1174L ALK G1202R ALK D1203N ALK amp	neuroblastoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, a neuroblastoma patient harboring ALK F1174L developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired ALK amplification, and ALK G1202R and D1203N each in cis with F1174L via circulating tumor DNA (PMID: 37147298; NCT03107988).	37147298
ALK F1174L ALK G1202R	neuroblastoma	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a neuroblastoma cell line harboring ALK F1174L and expressing G1202R was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298).	37147298
EML4 - ALK ALK F1174L ALK E1210K	lung adenocarcinoma	predicted - resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK E1210K was identified at the time of progression on Alunbrig (brigatinib) treatment in a patient with lung adenocarcinoma who initially harbored EML4-ALK (e13:e20) and ALK G1269A, and also acquired ALK F1174L and lost ALK G1269A during Alunbrig (brigatinib) treatment (PMID: 35123209).	35123209
ALK F1174L HRAS Q61L	neuroblastoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, HRAS Q61L was identified in a post-progression biopsy in a pediatric patient with metastatic neuroblastoma harboring ALK F1174L, who previously achieved a partial response on Lorbrena (lorlatinib) treatment (PMID: 39177282).	39177282
ALK rearrange	lung non-small cell carcinoma	no benefit	Erlotinib	Guideline	Actionable	EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	no benefit	Afatinib	Guideline	Actionable	EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Brigatinib	Guideline	Actionable	Alunbrig (brigatinib) is included in guidelines as preferred first-line and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Brigatinib	Guideline	Actionable	Alunbrig (brigatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 30285222; ESMO.org).	detail... 30285222
ALK rearrange	lung non-small cell carcinoma	sensitive	Brigatinib	Guideline	Actionable	Alunbrig (brigatinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as subsequent therapy for patients who have progressed on second-generation ALK inhibitors (PMID: 30596843; ESMO.org).	30596843 detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Brigatinib	Phase Ib/II	Actionable	In a Phase I/II trial, Alunbrig (brigatinib) treatment resulted in an objective response rate of 100% (8/8) in ALK inhibitor-naive, ALK-rearranged non-small cell lung cancer (NSCLC) patients, 72% (51/71) in Xalkori (crizotinib) treated ALK-rearranged NSCLC patients, and 83% (5/6) in ALK-rearranged NSCLC patients with CNS metastases (PMID: 27836716; NCT01449461).	27836716
ALK rearrange	lung non-small cell carcinoma	sensitive	Brigatinib	FDA approved - Has Companion Diagnostic	Actionable	In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged (fusion) non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573).	detail... 28475456
ALK rearrange	lung non-small cell carcinoma	sensitive	Brigatinib	FDA approved - Has Companion Diagnostic	Actionable	In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501).	detail... detail... detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Brigatinib	Clinical Study	Actionable	In a retrospective analysis, Alunbrig (brigatinib) demonstrated limited efficacy, resulting in an objective response rate of 17% (3/18) and stable disease in 50% (9/18) of patients with Alecensa (alectinib) refractory, ALK-positive non-small cell lung cancer, with a median progression-free survival of 4.4 months (PMID: 29935304).	29935304
ALK rearrange	lung non-small cell carcinoma	sensitive	Brigatinib	Clinical Study - Cohort	Actionable	In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alunbrig (brigatinib), and radiotherapy (PMID: 26438117).	26438117
ALK rearrange	anaplastic large cell lymphoma	sensitive	Brigatinib	Guideline	Actionable	Alunbrig (brigatinib) is included in guidelines as initial, second-line, and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org).	detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Brigatinib	Guideline	Actionable	Alunbrig (brigatinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org).	detail...
ALK rearrange	Cancer of Unknown Primary	sensitive	Brigatinib	Guideline	Actionable	Alunbrig (brigatinib) is included in guidelines for patients with cancer of unknown primary harboring ALK rearrangements (PMID: 36563965, PMID: 30285222; ESMO.org).	30285222 detail... 36563965
ALK rearrange	Advanced Solid Tumor	sensitive	ASP3026	Phase I	Actionable	In a Phase I trial, ASP3026 treatment resulted in a partial response in 50% (8/16) and stable disease in 44% (7/16) of patients with an advanced solid tumor harboring an ALK rearrangement or ALK F1174L (PMID: 26966027; NCT01284192).	26966027
ALK rearrange	lung non-small cell carcinoma	no benefit	Osimertinib	Guideline	Actionable	EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Alectinib	Guideline	Actionable	Alecensa (alectinib) is included in guidelines as preferred first-line therapy and as subsequent therapy for patients with ALK-rearranged advanced or metastatic non-small cell lung cancer (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Alectinib	Guideline	Actionable	Alecensa (alectinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 30285222; ESMO.org).	30285222 detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Alectinib	Guideline	Actionable	Alecensa (alectinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as first-line therapy for non-small cell lung cancer patients with ALK rearrangements, including patients with CNS involvement, and as subsequent therapy for patients that progress on Xalkori (crizotinib) (PMID: 30596843; ESMO.org).	30596843 detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in disease stability in an HIV-positive pregnant patient with non-small cell lung cancer harboring an ALK translocation, with normal fetal development observed (PMID: 36644155).	36644155
ALK rearrange	lung non-small cell carcinoma	sensitive	Alectinib	Phase II	Actionable	In a Phase II trial, Alecensa (alectinib) treatment was effective in treating non-small cell lung cancer patients with ALK rearrangement, resulting in a 50% (61/122) objective response rate (ORR) in all patients, a 45% (43/96) ORR in Crizotinib-refractory patients, and an 83% (70/84) CNS disease control rate (PMID: 26598747).	26598747
ALK rearrange	lung non-small cell carcinoma	sensitive	Alectinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in non-small cell lung cancer patients harboring ALK rearrangement (PMID: 28586279; NCT02075840).	28586279 detail... detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Alectinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase III trial supporting FDA approval (ALINA), adjuvant Alecensa (alectinib) treatment improved 2-year disease-free survival rate (93.8% vs 63.0%, HR 0.24, p<0.001) compared to chemotherapy in patients with resected non-small cell lung cancer harboring ALK rearrangement, and was associated with CNS disease-free survival benefit (HR 0.22) (PMID: 38598794; NCT03456076).	38598794 detail... detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Alectinib	Clinical Study - Cohort	Actionable	In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alecensa (alectinib), and radiotherapy (PMID: 26438117).	26438117
ALK rearrange	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response in a pregnant patient with ALK-rearranged metastatic lung adenocarcinoma, with normal fetal development and infant development for at least the first 20 months post birth (PMID: 33795207).	33795207
ALK rearrange	anaplastic large cell lymphoma	sensitive	Alectinib	Guideline	Actionable	Alecensa (alectinib) is included in guidelines as second-line and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org).	detail...
ALK rearrange	large cell neuroendocrine carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response lasting 9 months in a patient with metastatic large-cell neuroendocrine carcinoma of the lung harboring an ALK rearrangement (PMID: 37456922).	37456922
ALK rearrange	large cell neuroendocrine carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response with regression of lesions, including metastatic brain lesions, in a patient with large cell neuroendocrine carcinoma of the lung harboring an ALK rearrangement (PMID: 33352665).	33352665
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Alectinib	Guideline	Actionable	Alecensa (alectinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org).	detail...
ALK rearrange	epithelioid inflammatory myofibroblastic sarcoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response lasting 44.2 months in a pediatric patient with an ALK-rearranged epithelioid inflammatory myofibroblastic tumor (PMID: 34036223).	34036223
ALK rearrange	Cancer of Unknown Primary	sensitive	Alectinib	Guideline	Actionable	Alecensa (alectinib) is included in guidelines for patients with cancer of unknown primary harboring ALK rearrangements (PMID: 36563965, PMID: 30285222; ESMO.org).	detail... 30285222 36563965
ALK rearrange	colon mucinous adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) therapy resulted in a partial response in a patient with colon mucinous carcinoma harboring ALK rearrangement with a response duration of 103.3 weeks (PMID: 29352732; NCT00939770).	29352732
ALK rearrange	lung non-small cell carcinoma	sensitive	Crizotinib	Clinical Study	Actionable	In a clinical study, Xalkori (crizotinib) treatment resulted in an objective response rate of 59.3% (48/81, 8 complete responses), clinical benefit rate of 86.4% (70/81), median duration of response of 13.5 months, median progression-free survival of 15.8 months, and median overall survival of 46.5 months in patients with non-small cell lung cancer harboring an ALK rearrangement (PMID: 36162227; NCT02679170).	36162227
ALK rearrange	lung non-small cell carcinoma	sensitive	Crizotinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140).	detail... 25470694 detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Crizotinib	Phase III	Actionable	In a Phase III trial (PROFILE 1014), Xalkori (crizotinib) treatment resulted in improved progression-free survival (PFS) (PFS=10.9 months, n=172) relative to chemotherapy (PFS=7.0 months, n=171) in NSCLC patients with ALK rearrangements, including patients with and without brain metastases at baseline, and improved intracranial disease rate in patients with brain metastases at baseline (PMID: 27022118; NCT01154140).	27022118
ALK rearrange	lung non-small cell carcinoma	sensitive	Crizotinib	Phase III	Actionable	In a Phase III trial, Xalkori (crizotinib) treatment resulted in improved objective response (87.5%, 90/103 vs 45.6%, 47/103) and median progression free survival (11.1 vs 6.8 mo) compared to pemetrexed, cisplatin and carboplatinin combination treatment in treatment-naive ALK positive advanced non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9058); NCT01639001).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines as first-line therapy for ALK rearranged non-small cell lung cancer (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement, or as a next-line therapy in patients with ALK-rearranged non-small cell lung cancer who have not received prior Xalkori (crizotinib) (PMID: 30285222; ESMO.org).	30285222 detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as first-line therapy for non-small cell lung cancer patients with ALK rearrangements (PMID: 30596843; ESMO.org).	detail... 30596843
ALK rearrange	medullary thyroid carcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) therapy resulted in a partial response in a patient with medullary thyroid carcinoma harboring ALK rearrangement with a response duration of 16.1 weeks (PMID: 29352732; NCT00939770).	29352732
ALK rearrange	renal cell carcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response in a patient with metastatic renal cell carcinoma harboring an ALK rearrangement (PMID: 33457258).	33457258
ALK rearrange	anaplastic large cell lymphoma	sensitive	Crizotinib	FDA approved	Actionable	In a Phase I/II trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate (ORR) of 83% (5/6, all complete responses (CR)) at the 165 mg dose, and an ORR of 90% (18/20, 16 CR) at the 280 mg dose, in pediatric patients 1 years of age or older and young adults with relapsed or refractory ALK-positive anaplastic large cell lymphoma (PMID: 28787259; NCT00939770).	28787259 detail...
ALK rearrange	anaplastic large cell lymphoma	sensitive	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines as second-line and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org).	detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response after 6 months and a complete response in the second year of treatment in an 8-year-old pediatric patient with metastatic inflammatory myofibroblastic tumor harboring an ALK rearrangement, with response ongoing after 5 years of treatment (PMID: 31615346).	31615346
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response lasting 40 months in a pediatric patient with an ALK-rearranged inflammatory myofibroblastic tumor (PMID: 34036223).	34036223
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Crizotinib	FDA approved	Actionable	In a Phase I/II trial (Study ADVL0912) that supported FDA approval, Xalkori (crizotinib) therapy was safe and resulted in an objective response rate of 86% (12/14, 5 complete responses, 7 partial responses) and stable disease in 14% (2/14) of pediatric patients with ALK-positive unresectable inflammatory myofibroblastic tumors, with a median duration of response of 1.63 years (PMID: 28787259; NCT00939770).	28787259 detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Crizotinib	FDA approved	Actionable	In a Phase Ib trial (PROFILE 1013) that supported FDA approval, treatment with Xalkori (crizotinib) resulted in an objective response rate of 66.7% (6/9, 1 complete response, 5 partial responses) and stable disease in 33.3% (3/9) of adult patients with advanced ALK-positive inflammatory myofibroblastic tumors, with a median duration of response of 74.1 weeks in (PMID: 29352732; NCT00939770).	29352732 detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org).	detail...
ALK rearrange	lymphoma	predicted - sensitive	Crizotinib	Phase I	Actionable	In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) treatment resulted in an objective response rate of 52.9% (9/17, 8 complete responses, 1 partial response) and stable disease in 17.6% (3/17) of patients with advanced ALK-positive lymphomas, with a median duration of response of 135.9 weeks in (PMID: 29352732; NCT00939770).	29352732
ALK rearrange	Cancer of Unknown Primary	sensitive	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines for patients with cancer of unknown primary harboring ALK rearrangements (PMID: 36563965, PMID: 30285222; ESMO.org).	detail... 30285222 36563965
ALK rearrange	lung non-small cell carcinoma	no benefit	Gefitinib	Guideline	Actionable	EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Ceritinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase I trial that supported FDA approval, Zykadia (ceritinib) resulted in a blinded independent review committee (BIRC)-assessed objective response rate of 44% (72/163) and a duration of response of 7.1 months in ALK-rearranged non-small cell lung cancer patients (PMID: 25754348; NCT01283516).	25754348 detail... detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Ceritinib	Phase II	Actionable	In a Phase II trial (ASCEND-2), non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement and previously treated with Xalkori (crizotinib) and chemotherapy demonstrated an overall response rate of 38.6% (54/140), a disease control rate of 77.1%, a median time to response of 1.8 months, a median duration of response of 9.7 months, and a median progression-free survival of 5.7 months when treated with Zykadia (ceritinib) (PMID: 27432917; NCT01685060).	27432917
ALK rearrange	lung non-small cell carcinoma	sensitive	Ceritinib	Phase II	Actionable	In a Phase II trial (ASCEND-7), Zykadia (ceritinib) demonstrated efficacy in ALK-positive non-small cell lung cancer patients with active brain metastasis, resulting in whole-body overall response rate (ORR) of 35.7% (15/42), 30.0% (12/40), 50.0% (6/12), and 59.1% (26/44) in those who received prior radiation/ALK inhibitor (ALKi), ALKi only, radiation only, no prior radiation/ALKi, respectively, and whole-body ORR of 16.7% (3/18) in patients with leptomeningeal carcinomatosis (PMID: 35091443; NCT02336451).	35091443
ALK rearrange	lung non-small cell carcinoma	sensitive	Ceritinib	Clinical Study - Cohort	Actionable	In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated a median overall survival of 49.5 months following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Zykadia (ceritinib), and radiotherapy (PMID: 26438117).	26438117
ALK rearrange	lung non-small cell carcinoma	sensitive	Ceritinib	Guideline	Actionable	Zykadia (ceritinib) is included in guidelines as first-line and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Ceritinib	Guideline	Actionable	Zykadia (ceritinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 30285222; ESMO.org).	detail... 30285222
ALK rearrange	lung non-small cell carcinoma	sensitive	Ceritinib	Guideline	Actionable	Zykadia (ceritinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as first-line therapy for non-small cell lung cancer patients with ALK rearrangements, including patients with CNS involvement, and as subsequent therapy for patients that progress on Xalkori (crizotinib) (PMID: 30596843; ESMO.org).	detail... 30596843
ALK rearrange	anaplastic large cell lymphoma	sensitive	Ceritinib	Phase I	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 75% (6/8; 2 complete responses, 4 partial responses) and a disease control rate of 88% (7/8) in pediatric patients with anaplastic large cell lymphoma harboring ALK rearrangement, with median progression-free survival not reached (PMID: 34780709; NCT01742286).	34780709
ALK rearrange	anaplastic large cell lymphoma	sensitive	Ceritinib	Guideline	Actionable	Zykadia (ceritinib) is included in guidelines as initial, second-line, and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org).	detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Ceritinib	Phase I	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 70% (7/10; 7 partial responses) and a disease control rate of 80% (8/10) in pediatric patients with inflammatory myofibroblastic tumor harboring ALK rearrangement, with median progression-free survival not reached (PMID: 34780709; NCT01742286).	34780709
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Ceritinib	Guideline	Actionable	Zykadia (ceritinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org).	detail...
ALK rearrange	lung non-squamous non-small cell carcinoma	sensitive	Ceritinib	Phase III	Actionable	In a Phase III trial, first-line treatment with Zykadia (ceritinib) resulted in an improved median progression-free survival of 16.6 months, compared to 8.1 months with chemotherapy, in patients with ALK-rearranged non-squamous non-small cell lung cancer (PMID: 28126333; NCT01828099).	28126333
ALK rearrange	Cancer of Unknown Primary	sensitive	Ceritinib	Guideline	Actionable	Zykadia (ceritinib) is included in guidelines for patients with cancer of unknown primary harboring ALK rearrangements (PMID: 36563965, PMID: 30285222; ESMO.org).	detail... 30285222 36563965
ALK rearrange	lung non-small cell carcinoma	sensitive	Lorlatinib	Phase I	Actionable	In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in an objective response in 46% (19/41) of patients with non-small cell lung carcinoma harboring an ALK rearrangement (PMID: 29074098; NCT03052608).	29074098
ALK rearrange	lung non-small cell carcinoma	sensitive	Lorlatinib	Phase Ib/II	Actionable	In a Phase I/II trial, Lorbrena (lorlatinib) treatment resulted in an objective response rate (ORR) of 82.4% (14/17, all partial responses (PR)) and 63.6% (21/33, all PR) in Asian and non-Asian patients with ALK-positive non-small cell lung cancer who had prior Xalkori (crizotinib) treatment and an ORR of 47.2% (25/53, 2 complete responses, 23 PR) and 30.1% (22/73, all PR) in patients previously treated with any second-generation ALK inhibitor (PMID: 35660971; NCT01970865).	35660971
ALK rearrange	lung non-small cell carcinoma	sensitive	Lorlatinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865).	detail... detail... 30413378
ALK rearrange	lung non-small cell carcinoma	sensitive	Lorlatinib	Phase II	Actionable	In a Phase II trial, Lorbrena (lorlatinib) treatment resulted in an intracranial disease control rate of 95% (21/22), intracranial objective response rate of 59% (13/22; 6 complete responses, 7 partial responses), a median intracranial progression-free survival (PFS) rate of 24.6 months, and a 12-month PFS rate of 79% in patients with ALK-rearranged non-small cell lung cancer, who previously demonstrated central nervous system progression on second-generation ALK inhibitors (PMID: 35584349; NCT02927340).	35584349
ALK rearrange	lung non-small cell carcinoma	sensitive	Lorlatinib	Phase III	Actionable	In a Phase III trial (CROWN), Lorbrena (lorlatinib) treatment (n=149) demonstrated superior efficacy compared to Xalkori (crizotinib) (n=147) at 5-year follow-up in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients, with improved median progression-free survival (PFS, not reached vs 9.1 months, HR 0.19), 5-year PFS rate (60% vs 8%), and median time to intracranial progression (not reached vs 16.4 months) (PMID: 38819031; NCT03052608).	38819031
ALK rearrange	lung non-small cell carcinoma	sensitive	Lorlatinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase III trial (Study B7461006) that supported FDA approval, first-line Lorbrena (lorlatinib) treatment resulted in a significantly improved 12-mo progression-free survival rate (78% vs 39%, HR 0.28, p<0.0010) and a response rate of 76% (113/149) vs 58% (85/147) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer, and led to an intracranial response rate of 71% (12/14) vs 23% (3/13) in patients with measurable CNS metastases (PMID: 33207094; NCT03052608).	33207094 detail... detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in guidelines as preferred first-line therapy and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement who have progressed on an ALK tyrosine kinase inhibitor (PMID: 30285222; ESMO.org).	30285222 detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as subsequent therapy for patients who have progressed on second-generation ALK inhibitors (PMID: 30596843; ESMO.org).	30596843 detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	no benefit	Belizatinib	Phase I	Actionable	In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488).	31217479
ALK rearrange	Advanced Solid Tumor	sensitive	Belizatinib	Phase Ib/II	Actionable	In a Phase I trial, Belizatinib (TSR-011) treatment resulted in a response in 100% (3/3) of patients with ALK-rearranged advanced solid tumors when administered at higher doses, and stable disease for 7 months or longer in 56% (5/9) of patients at a lower dose (J Clin Oncol 33, 2015 (suppl; abstr 8063)).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Ensartinib	Guideline	Actionable	Ensartinib (X-396) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 30285222, Version Update 15 Sept 2020; ESMO.org).	detail... 30285222
ALK rearrange	lung non-small cell carcinoma	sensitive	Ensartinib	Phase Ib/II	Actionable	In a Phase I/II trial, Ensartinib (X-396) treatment resulted in partial response in 60% (36/60) and stable disease in 21.7 % (13/60) of patients with ALK-positive non-small cell lung cancer, with a median progression-free survival of 9.2 months, and a response rate of 80% (12/15) in crizotinib-naïve patients and 69% (20/29) in patients with prior crizotinib treatment (PMID: 29563138; NCT01625234).	29563138
ALK rearrange	lung non-small cell carcinoma	sensitive	Ensartinib	Phase III	Actionable	In a Phase III trial, Ensartinib (X-396) treatment significantly improved progression-free survival in patients with ALK-positive non-small cell lung cancer (25.8 vs 12.7 mo, HR 0.51, p<0.001) compared to Xalkori (crizotinib), and resulted in an intracranial response rate of 63.6% (7 of 11) in patients with target brain metastases at baselinewith compared to 21.1% (4 of 19) with Xalkori (crizotinib) (PMID: 34473194; NCT02767804).	34473194
ALK rearrange	lung non-small cell carcinoma	sensitive	Ensartinib	Clinical Study - Cohort	Actionable	In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Ensartinib (X-396), and radiotherapy (PMID: 26438117).	26438117
ALK rearrange	lung non-small cell carcinoma	no benefit	Atezolizumab	Guideline	Actionable	Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	no benefit	Atezolizumab	Clinical Study - Cohort	Actionable	In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694).	27225694
ALK rearrange	lung non-small cell carcinoma	no benefit	Nivolumab	Guideline	Actionable	Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	no benefit	Nivolumab	Clinical Study - Cohort	Actionable	In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694).	27225694
ALK rearrange	lung non-small cell carcinoma	no benefit	Durvalumab	Guideline	Actionable	Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	no benefit	Durvalumab	Clinical Study - Cohort	Actionable	In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Imfinzi (durvalumab), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694).	27225694
ALK rearrange	lung non-small cell carcinoma	no benefit	Pembrolizumab	Guideline	Actionable	Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	no benefit	Pembrolizumab	Clinical Study - Cohort	Actionable	In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694).	27225694
ALK rearrange	Advanced Solid Tumor	predicted - sensitive	Entrectinib	Clinical Study	Actionable	In a combined analysis of 2 Phase I trials (ALKA-372-001, STARTRK-1), Rozlytrek (entrectinib) treatment resulted in an objective response rate of 57% (4/7) in patients with ALK-rearranged advanced solid tumors that were treatment-naive, but no response (0/19) in patients who received prior Alk inhibitor treatments (PMID: 28183697; NCT02097810).	28183697
ALK rearrange	lung non-small cell carcinoma	no benefit	Ipilimumab + Nivolumab	Guideline	Actionable	Immune checkpoint inhibitors including Keytruda (pembrolizumab), Tecentriq (atezolizumab), and the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) are not indicated for use as initial systemic therapy in non-small cell lung cancer patients harboring oncogenes, including ALK rearrangement (NCCN.org).	detail...
ALK rearrange	anaplastic large cell lymphoma	not applicable	N/A	Guideline	Diagnostic	ALK rearrangement aids in the diagnosis of anaplastic large cell lymphoma (NCCN.org).	detail...
ALK rearrange	anaplastic large cell lymphoma	not applicable	N/A	Guideline	Prognostic	The presence of ALK rearrangement is associated with a favorable prognosis in patients with anaplastic large cell lymphoma (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	predicted - sensitive	Ceritinib + Ribociclib	Phase Ib/II	Actionable	In a Phase I/II trial, Zykadia (ceritinib) and Kisqali (ribociclib) combination therapy demonstrated a manageable safety profile and resulted in an overall response rate of 37.0% (10/27; 1 complete response and 9 partial responses) with a median progression-free survival of 21.5 months in patients with advanced ALK-rearranged non-small cell lung cancer (PMID: 35298959).	35298959
ALK rearrange	lung non-small cell carcinoma	sensitive	Ceritinib + Crizotinib	Clinical Study - Cohort	Actionable	In a retrospective analysis of patients with ALK-rearrangement positive non-small cell lung cancer, the combined median progression-free survival for sequential treatment with Xalkori (crizotinib) and Zykadia (ceritinib) without intervening treatments was 17.0 months, and overall survival was 49.4 months (PMID: 25724526).	25724526
ALK rearrange	lung non-small cell carcinoma	no benefit	Crizotinib + Onalespib	Phase II	Actionable	In a Phase II trial, Onalespib (AT13387) and Xalkori (crizotinib) combination treatment did not significantly improve median progression free survival (269 vs 266 days) or objective response rate (55.4%, 38/68 vs 45.3%, 31/68) compared to Xalkori (crizotinib) single treatment in patients with non-small cell lung carcinoma harboring either an ALK mutation or ALK rearrangement (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Conteltinib	Phase I	Actionable	In a Phase I trial, Conteltinib (CT-707) demonstrated safety and efficacy in patients with ALK-positive non-small cell lung cancer, resulting in an overall response rate (ORR) of 53.3% (32/60), a disease control rate (DCR) of 80%, and a median progression-free survival of 9.26 months, with an ORR of 61.4% (25/39) and a DCR of 82.1% in ALK inhibitor-naive patients and an ORR of 33.3% (7/21) and a DCR of 76.2% (16/21) in patients previously treated with Xalkori (crizotinib) (PMID: 36424628; NCT02695550).	36424628
ALK rearrange	lung adenocarcinoma	predicted - sensitive	Conteltinib	Phase I	Actionable	In a Phase I trial, Conteltinib (CT-707) demonstrated safety and preliminary efficacy, resulting in an overall response rate of 77% (10/13, 1 complete response, 9 partial responses) and a disease control rate of 85% (11/13) in patients with ALK-rearranged lung adenocarcinoma (n=12) or malignant pleural mesothelioma (n=1), median progression-free survival was 13 months in patients with lung adenocarcinoma (PMID: 32181989).	32181989
ALK rearrange	malignant pleural mesothelioma	no benefit	Conteltinib	Case Reports/Case Series	Actionable	In a Phase I trial, Conteltinib (CT-707) treatment resulted in disease progression after 1 cycle in a patient with ALK-rearranged malignant pleural mesothelioma (PMID: 32181989).	32181989
ALK rearrange	lung non-small cell carcinoma	sensitive	Iruplinalkib	Phase I	Actionable	In a Phase I trial, Iruplinalkib (WX-0593) demonstrated safety and resulted in an objective response rate (ORR) of 56.6% (56/99; all partial responses) and a disease control rate (DCR) of 83.8% (83/99), and median duration of response and median progression-free survival were not reached in non-small cell lung cancer patients with an ALK or ROS1-rearrangement, with an ORR of 58.2% (53/91; all partial responses) and DCR of 85.7% (78/91) in patients with an ALK rearrangement (PMID: 35087031; NCT03389815).	35087031
ALK rearrange	lung non-small cell carcinoma	sensitive	Iruplinalkib	Phase II	Actionable	In a Phase II trial (INTELLECT), Iruplinalkib (WX-0593) treatment resulted in an IRC-assessed objective response rate (ORR) of 69.9% (102/146), investigator-assessed ORR of 63.0%, disease control rate of 94.5%, and median progression-free survival of 14.5 months in patients with ALK-positive, Crizotinib-resistant non-small cell lung cancer, and an intracranial ORR of 46% (41/90) and 64% (27/42) for patients with CNS metastases or measurable intracranial lesions, respectively (PMID: 36829154; NCT04641754).	36829154
ALK rearrange	lung non-small cell carcinoma	sensitive	Iruplinalkib	Phase III	Actionable	In a Phase III trial (INSPIRE), Iruplinalkib (WX-0593) treatment in ALK-positive non-small cell lung cancer patients resulted in a significantly improved median progression free survival (mPFS) of 27.7 months, improved objective response rate (ORR) of 93.0% (133/143), and intracranial ORR of 90.9% (10/11) compared to a mPFS of 14.6 months (HR=0.34, p<0.0001), ORR of 89.3% (133/149), and intracranial ORR of 60.0% (9/15) with Xalkori (crizotinib) treatment (PMID: 38280448; NCT04632758).	38280448
ALK rearrange	lung non-small cell carcinoma	predicted - sensitive	PLB1003	Phase I	Actionable	In a Phase Ia trial, PLB1003 demonstrated safety and preliminary efficacy, resulted in a disease control rate of 86% (12/14, 10 partial response, 2 stable disease) in patients with ALK-rearranged non-small cell lung cancer who progressed on or did not tolerate previous treatment (Journal of Thoracic Oncology, Volume 14, Issue 10, S651).	detail...
ALK rearrange	lung adenocarcinoma	predicted - sensitive	Bevacizumab + Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a lung adenocarcinoma patient with brain metastasis harboring an ALK rearrangement, who had progressed on single agent Lorbrena (lorlatinib) treatment, demonstrated a partial response when treated with a combination of Lorbrena (lorlatinib) and Avastin (bevacizumab), with a 68% decrease in tumor size in the brain and a total duration of disease control for 9.1 months (PMID: 33283131).	33283131
ALK rearrange	lung non-small cell carcinoma	predicted - sensitive	Foritinib	Phase Ib/II	Actionable	In a Phase I/II trial, Foritinib was well tolerated in ALK-positive non-small cell lung cancer patients, and resulted in a disease control rate (DCR) of 100% and median progression-free survival (PFS) of 33.1 mo in ALK inhibitor (ALKi)-naive and 22.1 mo in ALKi-pretreated patients in Phase I, and a DCR of 98.1% and 88.5%, and objective response rate of 92.3% and 65.4%, in ALKi-naive or crizotinib-pretreated patients, respectively, in Phase II (J Clin Oncol 40, 2022 (suppl 16; abs 9076); NCT04237805).	detail...
ALK rearrange	lung small cell carcinoma	predicted - sensitive	Alectinib + Irinotecan	Case Reports/Case Series	Actionable	In a clinical case study, treatment with the combination of Alecensa (alectinib) and Camptosar (irinotecan) resulted in a partial response with progression-free survival lasting longer than 6 months in a small cell lung carcinoma patient harboring an ALK rearrangement (PMID: 34729013).	34729013
ALK rearrange	Advanced Solid Tumor	predicted - sensitive	TQ-B3101	Phase I	Actionable	In a Phase I trial, TQ-B3101 treatment was well tolerated and resulted in an objective response rate (ORR) of 62.5% (15/24) in patients with ALK-positive, ROS1-positive, or MET-amplified advanced solid tumors, with an ORR of 62.5% (5/8) in patients with brain metastases (J Clin Oncol 38, 2020 (suppl 15; abstr e21705); NCT03019276).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	TQ-B3139	Phase III	Actionable	In a Phase III trial, TQ-B3139 (CT-711) improved median progression-free survival (24.87 vs 11.60 mo; HR=0.47, p<0.0001), objective response rate (ORR) (81.68% vs 70.68%, p=0.056), and median duration of response (DOR) (25.79 vs 11.14 mo; HR=0.50, p=0.0003) compared to Xalkori (crizotinib) in ALK-rearranged non-small cell lung cancer patients, and also improved CNS ORR (78.95% vs 23.81%) and CNS DOR (25.82 vs 7.39 mo, p=0.0030) in patients with baseline brain lesions (PMID: 37574511; NCT04009317).	37574511
ALK rearrange	lung non-small cell carcinoma	sensitive	Ficonalkib	Phase Ib/II	Actionable	In a Phase I/II trial, Ficonalkib (SY-3505) treatment was well tolerated and resulted in an objective response rate (ORR) of 47.5% (38/80, all partial responses (PR)), disease control rate of 92.5%, median duration of response of 9.23 months, and median progression-free survival of 7.95 months, and an intracranial ORR of 37.5% (12/32, 4 complete responses, 8 PR) and intracranial DCR of 100% (32/32) in Chinese patients with ALK-positive non-small cell lung cancer (PMID: 38295954; NCT05257512).	38295954
ALK rearrange ALK I1171T	lung non-small cell carcinoma	predicted - resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in progressive disease in a patient with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171T (PMID: 29935304).	29935304
ALK rearrange ALK I1171T	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK I1171T was identified in the post-progression biopsy of a non-small cell lung cancer patient harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304).	29935304
ALK rearrange ALK I1171T	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, ALK I1171T was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554).	detail...
ALK rearrange ALK I1171T	lung adenocarcinoma	resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement with ALK I1171T progressed on Alecensa (alectinib) therapy after 4 months and resistance was confirmed using cell culture with cells derived from the patient’s tumor (PMID: 25228534).	25228534
ALK rearrange ALK I1171T	lung adenocarcinoma	resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement with ALK I1171T progressed on Xalkori (crizotinib) therapy after 8 months and resistance was confirmed using cell culture with cells derived from the patient's tumor (PMID: 25228534).	25228534
ALK rearrange ALK C1156Y	lung non-small cell carcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung cancer patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed after 18.2 months, and was found to have acquired ALK C1156Y (PMID: 25724526).	25724526
ALK rearrange ALK C1156Y	lung adenocarcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK C1156Y was identified in biopsies at disease progression after 16 months of Lorbrena (lorlatinib) treatment in a patient with lung adenocarcinoma harboring ALK rearrangement, cells derived from patient's tumor were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938).	31585938
ALK rearrange ALK C1156Y	lung adenocarcinoma	sensitive	Lorlatinib + Saracatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, Saracatinib (AZD0530) and Lorbrena (lorlatinib) synergistically inhibited viability of cells derived from the tumor from a patient with lung adenocarcinoma harboring ALK rearrangement and an acquired ALK C1156Y in culture (PMID: 31585938).	31585938
ALK rearrange ALK C1156Y ALK L1198F	lung non-small cell carcinoma	resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK C1156Y ALK L1198F developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534).	29650534
ALK rearrange MAP2K1 K57N	lung non-small cell carcinoma	sensitive	Ceritinib + Selumetinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, NSCLC patient derived cells harboring an ALK rearrangement demonstrated resistance to Zykadia (ceritinib) due to the acquired mutation MAP2K1 K57N, however, sensitivity was restored to Zykadia (ceritinib) with the addition of Koselugo (selumetinib), resulting in decreased cell survival in culture and reduced tumor volume in xenograft models (PMID: 25394791).	25394791
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in progressive disease in a patient with ALK-rearranged non-small cell lung cancer refractory to Alecensa (alectinib) treatment, ALK G1202R was identified in post-brigatinib biopsy (PMID: 29935304).	29935304
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Brigatinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK G1202R was identified in 33% (23/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1202R was identified in a patient with ALK-rearranged non-small cell lung carcinoma after the disease progressed while on Xalkori (crizotinib) followed by Alecensa (alectinib) therapy (PMID: 27130468).	27130468
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1202R was identified in a patient with ALK-rearranged non-small cell lung carcinoma after the disease progressed while on Zykadia (ceritinib) followed by Alecensa (alectinib) therapy (PMID: 28285684).	28285684
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, ALK G1202R was identified in 13% (7/52) of patients with non-small cell lung cancer harboring an ALK rearrangement after disease progression on first-line Alecensa (alectinib), and in 32% (18/56) patients who responded to second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554).	detail...
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Alectinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK G1202R was identified in 37% (17/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542).	31358542
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Ceritinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK G1202R was identified in 33% (23/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK G1202R	lung non-small cell carcinoma	sensitive	Lorlatinib	Clinical Study	Actionable	In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK G1202R or ALK G1202del (n=28), with an objective response rate of 57% (16/28; 95% CI 37.0-76.0), a median duration of response of 7 months (95% CI 6.1-24.4), and a median progression-free survival of 8.2 months (95% CI 5.6-25.6) (PMID: 30892989; NCT01970865).	30892989
ALK rearrange ALK G1202R	lung non-small cell carcinoma	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in guidelines as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK G1202R (NCCN.org).	detail...
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Ensartinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK G1202R was identified in 33% (23/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK G1202R	lung non-small cell carcinoma	predicted - sensitive	Ficonalkib	Case Reports/Case Series	Actionable	In a Phase I/II trial, Ficonalkib (SY-3505) treatment was well tolerated and resulted in an objective response rate (ORR) of 47.5% (38/80, all partial responses (PR)), a disease control rate of 92.5%, median duration of response of 9.23 months, and median progression-free survival of 7.95 in Chinese patients with ALK-positive non-small cell lung cancer, with an ORR of 70% (7/10) in patients with ALK G1202R (PMID: 38295954; NCT05257512).	38295954
ALK rearrange RB1 C706F TP53 loss	lung small cell carcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, RB1 C706F and loss of exons 1-11 in TP53 were identified in the pericardium infiltrating small cell lung cancer that developed while on Lorlatinib (PF-06463922) treatment in a patient with ALK-rearranged non-small cell lung carcinoma (PMID: 28285684).	28285684
ALK rearrange ALK I1171N	lung non-small cell carcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical study, Alunbrig (brigatinib) treatment resulted in stable disease in 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171N (PMID: 29935304).	29935304
ALK rearrange ALK I1171N	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a de novo ALK I1171N mutation was identified in the liver metastasis site and circulating DNA of a non-small cell lung cancer patient harboring an ALK rearrangement after disease progression on Alecensa (alectinib) treatment (PMID: 27565911).	27565911
ALK rearrange ALK I1171N	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, ALK I1171N was identified in 6% (3/52) of patients with non-small cell lung cancer harboring an ALK rearrangement after disease progression on first-line Alecensa (alectinib) treatment (Ann of Oncol (2022) 33 (suppl_7): S448-S554).	detail...
ALK rearrange ALK G1123S	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in rapid response in a patient with ALK-rearranged lung adenocarcinoma with an acquired ALK G1123S mutation, whose disease had relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233).	26134233
ALK rearrange ALK G1123S	lung adenocarcinoma	predicted - resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1123S was identified as an acquired mutation in a patient with ALK-rearranged lung adenocarcinoma whose disease relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233).	26134233
ALK rearrange ALK T1151dup ALK G1269A	lung non-small cell carcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring an ALK rearrangement demonstrated a partial response with Xalkori (crizotinib) treatment, but then progressed after 10.8 months, and was found to harbor secondary resistance mutations, ALK T1151dup and ALK G1269A (PMID: 25724526).	25724526
ALK rearrange ALK amp	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, ALK amplification was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on first-line Alecensa (alectinib) treatment and in 4% (2/56) of patients after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554).	detail...
ALK rearrange ALK amp	lung non-small cell carcinoma	resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical study, three patients with non-small cell lung carcinoma co-harboring an ALK rearrangement and ALK amplification demonstrated resistance to Xalkori (crizotinib) treatment (PMID: 27432227).	27432227
ALK rearrange ALK amp	lung non-small cell carcinoma	resistant	Crizotinib	Case Reports/Case Series	Actionable	In a retrospective analysis, two non-small cell lung cancer patients harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and were found to have acquired ALK amplification (PMID: 25724526).	25724526
ALK rearrange ALK S1206Y	lung non-small cell carcinoma	resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung cancer patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed after 32 months, and was found to have acquired ALK S1206Y (PMID: 25724526).	25724526
ALK rearrange ALK S1206Y	lung non-small cell carcinoma	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK S1206Y in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784).	22277784
ALK rearrange ALK I1171N ALK L1198F	lung non-small cell carcinoma	resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, a non-small cell lung cancer patient harboring ALK I1171N and L1198F in cis in the context of EML4-ALK demonstrated primary resistance to Lorlatinib (PF-06463922) (PMID: 29650534).	29650534
ALK rearrange ALK I1171N ALK D1203N	lung non-small cell carcinoma	resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK I1171N and D1203N developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534).	29650534
ALK rearrange ALK G1202R ALK G1269A	lung non-small cell carcinoma	resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R ALK G1269A developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534).	29650534
ALK rearrange ALK G1202R ALK L1204V ALK G1269A	lung non-small cell carcinoma	resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, ALK G1269A and L1204V were identified as acquired mutations in an ALK-positive non-small cell lung cancer patient harboring ALK G1202R who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534).	29650534
ALK rearrange ALK D1203N ALK E1210K ALK G1269A	lung non-small cell carcinoma	resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, ALK G1269A was identified as an acquired mutation in an ALK-positive non-small cell lung cancer patient harboring ALK E1210K and D1203N, who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534).	29650534
ALK rearrange ALK V1180L	lung non-small cell carcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical study, Alunbrig (brigatinib) treatment resulted in 1 partial response and 1 stable disease in a total of 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK V1180L (PMID: 29935304).	29935304
ALK rearrange ALK V1180L	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, ALK V1180L was identified in 4% (2/52) of patients with non-small cell lung cancer harboring an ALK rearrangement after disease progression on first-line Alecensa (alectinib) treatment (Ann of Oncol (2022) 33 (suppl_7): S448-S554).	detail...
ALK rearrange ALK V1180L	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, ALK V1180L was identified in post-progression biopsies of 2 non-small cell lung cancer patients harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304).	29935304
ALK rearrange ALK V1180L	lung non-small cell carcinoma	predicted - resistant	Alectinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK V1180L was identified in 11% (5/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542).	31358542
ALK rearrange ALK D1203N	lung non-small cell carcinoma	predicted - resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK D1203N was identified at disease progression while on Alunbrig (brigatinib) treatment in a patient with ALK-positive non-small cell lung cancer (PMID: 29935304).	29935304
ALK rearrange ALK D1203N	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK D1203N was identified in 24% (7/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542).	31358542
ALK rearrange TP53 mut	lung non-small cell carcinoma	decreased response	Brigatinib	Clinical Study - Cohort	Actionable	In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039) (PMID: 30165392).	30165392
ALK rearrange TP53 mut	lung non-small cell carcinoma	decreased response	Alectinib	Clinical Study - Cohort	Actionable	In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039) (PMID: 30165392).	30165392
ALK rearrange TP53 mut	lung non-small cell carcinoma	decreased response	Crizotinib	Clinical Study - Cohort	Actionable	In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Xalkori (crizotinib) as a first line therapy or after chemotherapy vs. patients with wild-type TP53 (5.0 mo., n=22 vs. 14.0 mo., n=71; p<0.001), and a lower median overall survival (17.0 mo., n=13 vs. not reached n=50; p=0.049) (PMID: 30165392).	30165392
ALK rearrange TP53 mut	lung non-small cell carcinoma	decreased response	Ceritinib	Clinical Study - Cohort	Actionable	In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039), and a lower median overall survival with treatment with Zykadia (ceritinib) after Xalkori (crizotinib) of 7.0 mo. vs. 50.0 mo. in patients with wild-type TP53 (p=0.001) (PMID: 30165392).	30165392
ALK rearrange ALK E1210K	lung non-small cell carcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer demonstrated disease progression when treated with Xalkori (crizotinib) due to a secondary acquired resistance mutation, ALK E1210K (PMID: 27432227).	27432227
ALK rearrange ALK F1174X	lung non-small cell carcinoma	predicted - sensitive	Lorlatinib	Clinical Study	Actionable	In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK F1174X (n=12), with an objective response rate of 42% (5/12; 95% CI 15.0-72.0), a median duration of response not reached (NR), and a median progression-free survival of 7.4 months (95% CI 2.8-NR) (PMID: 30892989; NCT01970865).	30892989
ALK rearrange ALK G1202del	lung non-small cell carcinoma	predicted - sensitive	Lorlatinib	Clinical Study	Actionable	In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK G1202R or ALK G1202del (n=28), with an objective response rate of 57% (16/28; 95% CI 37.0-76.0), a median duration of response of 7 months (95% CI 6.1-24.4), and a median progression-free survival of 8.2 months (95% CI 5.6-25.6) (PMID: 30892989; NCT01970865).	30892989
ALK rearrange ALK I1171X	lung non-small cell carcinoma	predicted - resistant	Brigatinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK I1171X was identified in 24% (17/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK I1171X	lung non-small cell carcinoma	predicted - resistant	Alectinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK I1171X was identified in 26% (12/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542).	31358542
ALK rearrange ALK I1171X	lung non-small cell carcinoma	predicted - resistant	Ceritinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK I1171X was identified in 24% (17/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK I1171X	lung non-small cell carcinoma	predicted - sensitive	Lorlatinib	Clinical Study	Actionable	In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring I1171X (n=8), with an objective response rate of 75% (6/8; 95% CI 35.0-97.0), a median duration of response of 4.2 months (95% CI 2.8-4.2), and a median progression-free survival of 5.5 months (95% CI 4.1-6.9) (PMID: 30892989; NCT01970865).	30892989
ALK rearrange ALK I1171X	lung non-small cell carcinoma	predicted - resistant	Ensartinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK I1171X was identified in 24% (17/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542).	31358542
ALK rearrange ALK L1152R	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with ALK-rearranged lung adenocarcinoma, which also harbored RB1 deletion and TP53 G154V and R158C mutations, was found to have an acquired ALK L1152R mutation in a biopsy of a pleural nodule following progression on Xalkori (crizotinib) and Zykadia (ceritinib), and was subsequently treated with Alecensa (alectinib), resulting in a partial response in all disease areas (PMID: 27091190).	27091190
ALK rearrange ALK L1152R	lung adenocarcinoma	predicted - resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with ALK-rearranged lung adenocarcinoma, which also harbored RB1 deletion and TP53 G154V and R158C mutations, demonstrated a partial response following treatment with Zykadia (ceritinib), however, progressed after 4 months and was found to have an acquired ALK L1152R mutation in a biopsy of a pleural nodule (PMID: 27091190).	27091190
ALK rearrange ALK F1174C	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Clinical Study - Cohort	Actionable	In a retrospective study, ALK F1174C/L was identified in 14% (4/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542).	31358542
ALK rearrange ALK F1174C ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588).	31439588
ALK rearrange ALK T1151M ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588).	31439588
ALK rearrange ALK G1269A	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1269A was identified in biopsies at disease progression after 30 months of Xalkori (crizotinib) treatment in a patient with lung adenocarcinoma harboring ALK rearrangement (PMID: 31585938).	31585938
ALK rearrange ALK G1269A	lung non-small cell carcinoma	predicted - sensitive	Lorlatinib	Clinical Study	Actionable	In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK G1269A (n=9), with an objective response rate of 89% (8/9; 95% CI 52.0-100.0), a median duration of response not reached (NR) (95% CI 5.6-NR), and a median progression-free survival not reached (95% CI 8.2-NR) (PMID: 30892989; NCT01970865).	30892989
ALK rearrange ALK mut	lung non-small cell carcinoma	sensitive	Ceritinib	Clinical Study - Cohort	Actionable	In a retrospective analysis, patients with ALK-rearrangement positive non-small cell lung cancer who acquired ALK drug resistance mutations following Xalkori (crizotinib) treatment had a median progression-free survival (mPFS) of 5.4 months on Zykadia (ceritinib), which was not significantly different than the mPFS of 6.5 months for patients without ALK mutations (PMID: 25724526).	25724526
ALK rearrange ROS1 rearrange	lung non-small cell carcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in a near complete response and progression-free survival for at least 55 months in a patient with non-small cell lung cancer harboring rearrangements in ALK and ROS1 (PMID: 34459458).	34459458
ALK rearrange ROS1 rearrange	lung adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in decreased tumor size and metabolism in a patient with lung adenocarcinoma harboring rearrangements in ROS1 and ALK (PMID: 28532565).	28532565
ALK rearrange ROS1 rearrange	lung adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in decreased tumor size at 3 months in a patient with lung adenocarcinoma harboring rearrangements in ROS1 and ALK (PMID: 30327151).	30327151
ALK rearrange ROS1 rearrange	lung adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in lymph node response and progression-free survival greater than 1 year in a patient with EGFR wild-type lung adenocarcinoma harboring rearrangements in ALK and ROS1 (PMID: 29268402).	29268402
ALK rearrange ALK L1196Q	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, ALK L1196Q was identified in 4% (2/52) of patients with non-small cell lung cancer harboring an ALK rearrangement after progression on first-line Alecensa (alectinib) treatment (Ann of Oncol (2022) 33 (suppl_7): S448-S554).	detail...
ALK rearrange ALK E1129V	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, ALK E1129V was identified in 4% (2/56) of patients with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554).	detail...
ALK rearrange ALK I1171S	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, ALK I1171S was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554).	detail...
ALK rearrange ALK F1174V	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, ALK F1174V was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554).	detail...
ALK rearrange ALK F1174S	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, ALK F1174S was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554).	detail...
ALK rearrange ALK T1151R	lung adenocarcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in clinical improvement and a major response in tumor volume and metabolic activity in a patient with metastatic lung adenocarcinoma harboring an ALK rearrangement and ALK T1151R until disease progression 3 months later (PMID: 31027750).	31027750
ALK rearrange ALK T1151R	lung adenocarcinoma	predicted - resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK T1151R was identified on post-progression biopsy in a patient with lung adenocarcinoma harboring an ALK rearrangement who had been on Zykadia (ceritinib) treatment for 6 months (PMID: 31027750).	31027750
ALK rearrange ALK T1151M	lung non-small cell carcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a clinical case study, Ensartinib (X-396) treatment resulted in a partial response in a non-small cell lung cancer patient harboring a non-coding ALK rearrangement with ALK T1151M (PMID: 31446141).	31446141
ALK mutant	lung non-small cell carcinoma	no benefit	Belizatinib	Phase I	Actionable	In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488).	31217479
ALK mutant	lung non-small cell carcinoma	no benefit	Crizotinib + Onalespib	Phase II	Actionable	In a Phase II trial, Onalespib (AT13387) and Xalkori (crizotinib) combination treatment did not significantly improve median progression free survival (269 vs 266 days) or objective response rate (55.4%, 38/68 vs 45.3%, 31/68) compared to Xalkori (crizotinib) single treatment in patients with non-small cell lung carcinoma harboring either an ALK mutation or ALK rearrangement (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217).	detail...
ALK mut TP53 wild-type	neuroblastoma	sensitive	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in patient-derived neuroblastoma cell lines harboring Alk mutations and functional TP53, resulting in growth inhibition in culture and tumor regression in animal models (PMID: 26438783).	26438783
ALK G1128A	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing ALK G1128A was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722).	27049722
ALK G1128A	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) decreased Alk phosphorylation and neurite outgrowth in cells expressing ALK G1128A in culture (PMID: 31852910).	31852910
EML4 - ALK ALK G1128A ALK R1192P	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1128A and ALK R1192P were identified in the post-progression biopsy of a patient with lung adenocarcinoma harboring EML4-ALK who previously responded to treatment with Xalkori (crizotinib) (PMID: 30089600).	30089600
ALK I1171N	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing ALK I1171N was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722).	27049722
ALK I1171N	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) decreased Alk phosphorylation and neurite outgrowth in cells expressing ALK I1171N in culture (PMID: 31852910).	31852910
ALK I1171N	Advanced Solid Tumor	decreased response	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, ALK I1171N demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N	lung adenocarcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in stable disease with a progression-free survival of 17 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and ALK I1171N (PMID: 38623748).	38623748
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 35421578).	35421578
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171N	sarcoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a Phase II trial, ALK I1171N was identified on post-progression biopsy in a patient with metastatic non-myofibroblastic sarcoma harboring EML4-ALK (e2:e20), who previously achieved a partial response on Alecensa (alectinib) treatment (PMID: 39188081).	39188081
EML4 - ALK ALK I1171N	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated tumor regression when treated with Alecensa (alectinib), but progressed seven months later, and was found to harbor a secondary resistance mutation, ALK I1171N (PMID: 25393798).	25393798
EML4 - ALK ALK I1171N	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK I1171N was identified in the post-progression biopsy of a patient with non-small cell lung cancer harboring EML4-ALK who was treated with Alecensa (alectinib) (PMID: 33166721).	33166721
EML4 - ALK ALK I1171N	lung non-small cell carcinoma	predicted - resistant	Alectinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Alecensa (alectinib) failed to inhibit growth of patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture, and did not induce tumor regression or reduce Alk phosphorylation in xenograft models (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK I1171N was identified at the time of progression in a patient with metastatic lung adenocarcinoma harboring EML4-ALK who previously demonstrated a partial response on Alecensa (alectinib) treatment (PMID: 38623748).	38623748
EML4 - ALK ALK I1171N	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK I1171N was identified in post-progression biopsy in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e20), who previously responded to Alecensa (alectinib) (PMID: 36864442).	36864442
EML4 - ALK ALK I1171N	pulmonary neuroendocrine tumor	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK I1171N was identified in post-progression biopsy in a patient with metastatic pulmonary atypical carcinoid tumor harboring EML4-ALK (e6:e20) who previously responded to Alecensa (alectinib) treatment (PMID: 35832448).	35832448
EML4 - ALK ALK I1171N	inflammatory myofibroblastic tumor	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK I1171N was identified on post-progression biopsy in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK, who previously responded to Alecensa (alectinib) (PMID: 37255276).	37255276
EML4 - ALK ALK I1171N	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated resistance to treatment with Alecensa (alectinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171N	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	lung non-small cell carcinoma	resistant	Crizotinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	Advanced Solid Tumor	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171N	Advanced Solid Tumor	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	pulmonary neuroendocrine tumor	predicted - sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, Zykadia (ceritinib) treatment resulted in response after 1 month of treatment with tumor shrinkage in a patient with metastatic pulmonary atypical carcinoid tumor harboring EML4-ALK (e6:e20) and ALK I1171N (PMID: 35832448).	35832448
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	sarcoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with metastatic non-myofibroblastic sarcoma harboring EML4-ALK (e2:e20) and ALK I1171N (PMID: 39188081).	39188081
EML4 - ALK ALK I1171N	lung non-small cell carcinoma	sensitive	Lorlatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited cell viability, decreased downstream ALK signaling, and induced apoptosis in patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in all lesions including lesions within the CNS with a progression-free survival of 14 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and ALK I1171N (PMID: 38623748).	38623748
EML4 - ALK ALK I1171N	inflammatory myofibroblastic tumor	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in near resolution of the pleural effusion and decrease in pleural mass in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK and ALK I1171N (PMID: 37255276).	37255276
EML4 - ALK ALK I1171N	Advanced Solid Tumor	conflicting	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171N	Advanced Solid Tumor	conflicting	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N demonstrated resistance to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	lung adenocarcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a clinical case study, Ensartinib (X-396) treatment resulted in a decrease in the liver lesions after 20 days of treatment in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e20) and ALK I1171N (PMID: 36864442).	36864442
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ensartinib (X-396) inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 36201110).	36201110
EML4 - ALK ALK I1171N	lung non-small cell carcinoma	resistant	Entrectinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	lung non-small cell carcinoma	sensitive	Gilteritinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited growth of patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture, and induced tumor regression and suppressed Alk phosphorylation and downstream signaling in xenograft models (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N	Advanced Solid Tumor	resistant	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Augtyro (repotrectinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK I1171N	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 35421578).	35421578
EML4 - ALK ALK I1171N	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171N in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to TPX-0131 in culture (PMID: 36201110).	36201110
EML4 - ALK ALK I1171N	Advanced Solid Tumor	predicted - sensitive	NVL-655	Preclinical	Actionable	In a preclinical study, NVL-655 moderately inhibited viability cells expressing EML4-ALK and ALK I1171N in culture and inhibited tumor growth in a transplant model (PMID: 39269178).	39269178
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK I1171N was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorbrena (lorlatinib) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK G1269A	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 36201110).	36201110
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to Xalkori (crizotinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 36201110).	36201110
EML4 - ALK ALK I1171N ALK L1256F	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to TPX-0131 in culture (PMID: 36201110).	36201110
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	lung non-small cell carcinoma	predicted - resistant	Alectinib	Preclinical - Pdx	Actionable	In a preclinical study, Alecensa (alectinib) failed to inhibit tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Preclinical - Pdx	Actionable	In a preclinical study, Lorbrena (lorlatinib) failed to inhibit tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	lung non-small cell carcinoma	sensitive	Gilteritinib	Preclinical - Pdx	Actionable	In a preclinical study, Xospata (gilteritinib) induced complete tumor regression in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I, and also induced tumor regression when administered to separate PDX tumors which had demonstrated resistance to Alecensa (alectinib) or Lorbrena (lorlatinib) treatment (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK F1174I	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174I in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	predicted - resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198H	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198H in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F were resistant to Alecensa (alectinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	conflicting	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	conflicting	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	conflicting	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 35726063).	35726063
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F were resistant to Zykadia (ceritinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	predicted - resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F demonstrated resistance to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171N ALK L1198F	Advanced Solid Tumor	predicted - sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 moderately inhibited viability of cells expressing EML4-ALK, ALK I1171N, and ALK L1198F in culture (PMID: 39269178).	39269178
EML4 - ALK ALK I1171N ALK V1180L	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK, as well as IDH1 R132H, developed progressive disease after initial response to Alecensa (alectinib), and ALK I1171N and ALK V1180L were identified in the post-progression biopsy along with germline BRCA2 F2801fs (PMID: 35324529).	35324529
EML4 - ALK ALK I1171N ALK D1203N	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) did not inhibit viability of cells expressing EML4-ALK, ALK I1171N, and ALK D1203N in culture (PMID: 39269178).	39269178
EML4 - ALK ALK I1171N ALK D1203N	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) did not inhibit viability of cells expressing EML4-ALK, ALK I1171N, and ALK D1203N in culture (PMID: 39269178).	39269178
EML4 - ALK ALK I1171N ALK D1203N	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK D1203N were resistant to Alecensa (alectinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK I1171N ALK D1203N	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK D1203N were resistant to Xalkori (crizotinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK I1171N ALK D1203N	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) did not inhibit viability of cells expressing EML4-ALK, ALK I1171N, and D1203N in culture (PMID: 39269178).	39269178
EML4 - ALK ALK I1171N ALK D1203N	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) did not inhibit viability of cells expressing EML4-ALK, ALK I1171N, and ALK D1203N in culture (PMID: 39269178).	39269178
EML4 - ALK ALK I1171N ALK D1203N	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) did not inhibit viability of cells expressing EML4-ALK, ALK I1171N, and ALK D1203N in culture (PMID: 39269178).	39269178
EML4 - ALK ALK I1171N ALK D1203N	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK D1203N were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK I1171N ALK D1203N	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 did not inhibit viability of cells expressing EML4-ALK, ALK I1171N, and ALK D1203N in culture (PMID: 39269178).	39269178
EML4 - ALK ALK I1171N ALK D1203N	Advanced Solid Tumor	resistant	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 did not inhibit viability of cells expressing EML4-ALK, ALK I1171N, and ALK D1203N (PMID: 39269178).	39269178
EML4 - ALK ALK E1129V ALK I1171N	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and E1129V were resistant to Alecensa (alectinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK E1129V ALK I1171N	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and E1129V were resistant to Xalkori (crizotinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK E1129V ALK I1171N	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and E1129V were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK E1129V ALK I1171N	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and E1129V were resistant to TPX-0131 in culture (PMID: 36201110).	36201110
EML4 - ALK ALK C1156Y ALK I1171N	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and C1156Y were resistant to Alecensa (alectinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK C1156Y ALK I1171N	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and C1156Y were resistant to Xalkori (crizotinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK C1156Y ALK I1171N	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and C1156Y were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK C1156Y ALK I1171N	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK I1171N and C1156Y in culture (PMID: 36201110).	36201110
EML4 - ALK ALK C1156Y ALK I1171N	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and C1156Y were resistant to TPX-0131 in culture (PMID: 36201110).	36201110
ALK I1171N ALK pos	diffuse large B-cell lymphoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in an ongoing complete metabolic response 20 months post-transplant in a patient with an ALK-positive large B-cell lymphoma harboring ALK I1171N (PMID: 36809056).	36809056
EML4 - ALK ALK I1171N ALK G1202R	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a lung adenocarcinoma patient harboring EML4-ALK with ALK I1171N and G1202R, along with ALK-ENC1 (PMID: 37007089).	37007089
ALK I1171N ALK Y1278S	neuroblastoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a retrospective analysis, a neuroblastoma patient harboring ALK Y1278S progressed on treatment with Lorbrena (lorlatinib) and was found to have acquired ALK I1171N (PMID: 38787533; NCT04477681).	38787533
ALK F1245C	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing ALK F1245C was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722).	27049722
ALK F1245C	neuroblastoma	resistant	Crizotinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1245C in culture, and only delayed tumor growth in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404).	26554404
ALK F1245C	neuroblastoma	sensitive	Lorlatinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells over expressing ALK F1245C in culture, and induced rapid and sustained complete tumor regression in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404).	26554404
ALK F1245C	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells overexpressing ALK F1245C in culture (PMID: 26554404).	26554404
ALK F1245C	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK F1245C in culture (PMID: 27483357).	27483357
ALK F1245C	neuroblastoma	sensitive	Ceritinib + Ribociclib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of Zykadia (ceritinib) and Kisqali (ribociclib) inhibited proliferation in a neuroblastoma cell line harboring ALK F1245C in culture, and resulted in enhanced tumor growth inhibition compared to either Zykadia (ceritinib) or Kisqali (ribociclib) alone (P=0.04 and P<0.0001, respectively) and induced complete and sustained tumor regression in a patient-derived xenograft (PDX) model (PMID: 27986745).	27986745
ALK F1245C	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) decreased Alk phosphorylation and neurite outgrowth in cells expressing ALK F1245C in culture (PMID: 31852910).	31852910
ALK F1245C	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1245C in an in vitro assay (PMID: 34158340).	34158340
ALK F1245C TP53 wild-type	neuroblastoma	sensitive	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Pdx	Actionable	In a preclinical study, Xalkori (crizotinib) worked synergistically with Topotecan and Cytoxan (cyclophosphamide), resulting in sustained tumor regression in crizotinib-resistant neuroblastoma PDX models harboring ALK F1245C and wild-type Tp53 (PMID: 26438783).	26438783
EML4 - ALK ALK F1245C	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of a cell line expressing EML4-ALK with ALK F1245C in culture (PMID: 31446141).	31446141
EML4 - ALK ALK F1245C	lung non-small cell carcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung cancer patient harboring EML4-ALK variant 3 demonstrated an initial response to treatment with Xalkori (crizotinib), but progressed after 27 months and was found to have acquired ALK F1245C (PMID: 26775591).	26775591
EML4 - ALK ALK F1245C	lung non-small cell carcinoma	sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung cancer patient harboring EML4-ALK variant 3 that demonstrated resistance to treatment with Xalkori (crizotinib) after acquisition of ALK F1245C, achieved a complete radiographic response with no evidence of progression at 6 months following treatment with Zykadia (ceritinib) (PMID: 26775591).	26775591
EML4 - ALK ALK F1245C	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK F1245C in culture (PMID: 31446141).	31446141
ALK R1192P	malignant pheochromocytoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response (PR) after 2 months of therapy and a sustained PR at 10 months in a patient with malignant pheochromocytoma harboring ALK R1192P (PMID: 34371380).	34371380
ALK R1192P	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing ALK R1192P was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722).	27049722
ALK R1192P	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK R1192P in culture (PMID: 27483357).	27483357
ALK R1192P	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) decreased Alk phosphorylation and neurite outgrowth in cells expressing ALK R1192P in culture (PMID: 31852910).	31852910
ALK R1192P	malignant pheochromocytoma	no benefit	Alectinib + Octreotide	Case Reports/Case Series	Actionable	In a clinical case study, addition of Alecensa (alectinib) to Octreotide treatment did not lead to a response in a patient with malignant pheochromocytoma harboring ALK R1192P, with a radiological stable disease after 1 month of treatment and disease progression after 5 months of treatment (PMID: 34371380).	34371380
EML4 - ALK ALK R1192P	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859).	27009859
EML4 - ALK ALK R1192P	Advanced Solid Tumor	resistant	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK R1192P were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK R1192P	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells overexpressing EML4-ALK with ALK R1192P in culture (PMID: 27009859).	27009859
EML4 - ALK ALK R1192P	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859).	27009859
EML4 - ALK ALK R1192P	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK R1192P were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK R1192P	Advanced Solid Tumor	sensitive	AZD3463	Preclinical - Cell culture	Actionable	In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859).	27009859
ALK R1275Q	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, a transformed cell line expressing ALK R1275Q was sensitive to Alunbrig (brigatinib) in culture and in cell line xenograft models, resulting in cell growth inhibition (PMID: 27049722).	27049722
ALK R1275Q	neuroblastoma	conflicting	Crizotinib	Case Reports/Case Series	Actionable	In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, among the 12 patients harboring ALK R1275Q, 1 achieved a complete response, 2 achieved partial responses, and 2 achieved prolonged stable diseases (PMID: 33568345; NCT00939770).	33568345
ALK R1275Q	neuroblastoma	conflicting	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104).	38032104
ALK R1275Q	neuroblastoma	conflicting	Crizotinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK R1275Q in culture, and only delayed tumor growth in cell line xenograft models (PMID: 26554404).	26554404
ALK R1275Q	neuroblastoma	conflicting	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 29907598).	29907598
ALK R1275Q	neuroblastoma	conflicting	Crizotinib	Preclinical	Actionable	In a preclinical study, Xalkori (crizotinib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK R1275Q (corresponds to R1279Q in mouse) and subsequent upregulation of Ret (PMID: 24811913).	24811913
ALK R1275Q	neuroblastoma	sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment resulted in 3 partial responses and 1 stable disease in 7 pediatric patients with neuroblastoma harboring ALK R1275Q (PMID: 34780709; NCT01742286).	34780709
ALK R1275Q	neuroblastoma	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104).	38032104
ALK R1275Q	neuroblastoma	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 29907598).	29907598
ALK R1275Q	neuroblastoma	sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in 3 complete responses and 1 partial response in 4 pediatric patients with relapsed or refractory neuroblastoma harboring ALK R1275Q, with treatment ongoing for an average of 52 months (PMID: 39177282).	39177282
ALK R1275Q	neuroblastoma	sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in 3 of 4 patients with neuroblastoma harboring ALK R1275Q (PMID: 37561984).	37561984
ALK R1275Q	neuroblastoma	sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a complete response in a neuroblastoma patient harboring a germline ALK R1275Q, who was on treatment for 18 months and remained in remission at 5 years (PMID: 37147298; NCT03107988).	37147298
ALK R1275Q	neuroblastoma	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104).	38032104
ALK R1275Q	neuroblastoma	sensitive	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation, resulted in growth inhibition of neuroblastoma cells over expressing ALK R1275Q in culture and induced rapid and sustained complete tumor regression in cell line xenograft models (PMID: 26554404).	26554404
ALK R1275Q	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells overexpressing ALK R1275Q in culture (PMID: 26554404).	26554404
ALK R1275Q	neuroblastoma	no benefit	Belizatinib	Case Reports/Case Series	Actionable	In a Phase I trial, a neuroblastoma patient harboring ALK R1275Q did not respond to treatment with Belizatinib (TSR-011) (PMID: 31217479; NCT02048488).	31217479
ALK R1275Q	neuroblastoma	sensitive	Vandetanib	Preclinical	Actionable	In a preclinical study, Caprelsa (vandetanib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK R1275Q (corresponds to R1279Q in mouse) and subsequent upregulation of Ret (PMID: 24811913).	24811913
ALK R1275Q	neuroblastoma	predicted - sensitive	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ensartinib (X-396) treatment resulted in inhibition of cell proliferation in a neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 34482287).	34482287
ALK R1275Q	neuroblastoma	sensitive	CEP-28122	Preclinical - Cell culture	Actionable	In a preclinical study, CEP-28122 inhibited growth of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 22203728).	22203728
ALK R1275Q	neuroblastoma	sensitive	Ceritinib + Ribociclib	Preclinical - Cell culture	Actionable	In a preclinical study, the combination of Zykadia (ceritinib) and Kisqali (ribociclib) synergistically inhibited proliferation and Alk phosphorylation and induced cell cycle arrest in neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 27986745).	27986745
ALK R1275Q	neuroblastoma	sensitive	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in human neuroblastoma cell line xenograft models harboring ALK R1275Q and wild-type TP53 (PMID: 26438783).	26438783
ALK R1275Q	neuroblastoma	predicted - sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) treatment resulted in inhibition of cell proliferation in a neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 34482287).	34482287
ALK R1275Q	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) decreased Alk phosphorylation and neurite outgrowth in cells expressing ALK R1275Q in culture (PMID: 31852910).	31852910
ALK R1275Q	neuroblastoma	sensitive	SHP099	Preclinical - Cell culture	Actionable	In a preclinical study, SHP099 decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104).	38032104
ALK R1275Q	Advanced Solid Tumor	predicted - sensitive	Conteltinib	Preclinical - Biochemical	Actionable	In a preclinical study, Conteltinib (CT-707) inhibited ALK R1275Q activity in an in vitro assay (PMID: 36424628).	36424628
ALK R1275Q	neuroblastoma	sensitive	TNO155	Preclinical - Cell culture	Actionable	In a preclinical study, TNO155 decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104).	38032104
ALK R1275Q	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK R1275Q in an in vitro assay (PMID: 34158340).	34158340
ALK R1275Q	neuroblastoma	sensitive	Crizotinib + SHP099	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of SHP099 and Xalkori (crizotinib) synergistically decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104).	38032104
ALK R1275Q	neuroblastoma	sensitive	Ceritinib + TNO155	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of TNO155 and Zykadia (ceritinib) synergistically decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104).	38032104
ALK R1275Q	neuroblastoma	sensitive	Lorlatinib + TNO155	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of TNO155 and Lorbrena (lorlatinib) synergistically decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104).	38032104
ALK R1275Q	neuroblastoma	sensitive	Crizotinib + TNO155	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of TNO155 and Xalkori (crizotinib) synergistically decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104).	38032104
ALK R1275Q	neuroblastoma	sensitive	Ceritinib + SHP099	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of SHP099 and Zykadia (ceritinib) synergistically decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104).	38032104
ALK R1275Q	neuroblastoma	sensitive	Lorlatinib + SHP099	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of SHP099 and Lorbrena (lorlatinib) synergistically decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104).	38032104
ALK R1275Q TP53 wild-type	neuroblastoma	sensitive	Ceritinib + CGM097	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of Zykadia (ceritinib) and CGM097 inhibited Alk signaling and resulted in synergistic inhibition of proliferation in a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture and induced tumor regression in a cell line xenograft model (PMID: 28425916).	28425916
ALK R1275Q TP53 wild-type	neuroblastoma	sensitive	Idasanutlin + TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, the combination of TAE684 and Idasanutlin (RG7388) inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 36602782).	36602782
ALK R1275Q TP53 wild-type	neuroblastoma	sensitive	Alectinib + Idasanutlin	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 36602782).	36602782
EML4 - ALK ALK R1275Q	Advanced Solid Tumor	sensitive	APG-2449	Preclinical - Cell culture	Actionable	In a preclinical study, APG-2449 inhibited proliferation of cells expressing EML4-ALK with ALK R1275Q in culture (PMID: 35820889).	35820889
EML4 - ALK ALK R1275Q	Advanced Solid Tumor	sensitive	TQ-B3139	Preclinical - Cell culture	Actionable	In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of cells expressing EML4-ALK with ALK R1275Q in culture (PMID: 30210922).	30210922
ALK G1202R ALK R1275Q	neuroblastoma	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a neuroblastoma cell line harboring ALK R1275Q and expressing G1202R was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298).	37147298
ALK G1202R ALK R1275Q BRAF V600E	neuroblastoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, a neuroblastoma patient harboring ALK R1275Q developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired ALK G1202R and BRAF V600E via circulating tumor DNA (PMID: 37147298; NCT03107988).	37147298
ALK S1206Y	Advanced Solid Tumor	predicted - sensitive	APG-2449	Preclinical - Biochemical	Actionable	In a preclinical study, APG-2449 inhibited the kinase activity of ALK S1206Y in culture (PMID: 35820889).	35820889
EML4 - ALK ALK S1206Y	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK S1206Y in the context of EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK S1206Y	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated moderate resistance to Alunbrig (brigatinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK S1206Y	Advanced Solid Tumor	resistant	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated moderate resistance to ASP3026 in culture (PMID: 25727400).	25727400
EML4 - ALK ALK S1206Y	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK S1206Y in culture and in xenograft models (PMID: 24887559).	24887559
EML4 - ALK ALK S1206Y	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated moderate resistance to Alecensa (alectinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK S1206Y	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK S1206Y	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated growth inhibition with Zykadia (ceritinib) treatment in culture (PMID: 24675041).	24675041
EML4 - ALK ALK S1206Y	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK S1206Y in culture (PMID: 25727400).	25727400
EML4 - ALK ALK S1206Y	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK S1206Y in the context of EML4-ALK in culture (PMID: 26144315).	26144315
EML4 - ALK ALK S1206Y	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK S1206Y in culture (PMID: 31446141).	31446141
EML4 - ALK ALK S1206Y	Advanced Solid Tumor	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK and ALK S1206Y in culture (PMID: 39269178).	39269178
ALK fusion ALK S1206Y	lung non-small cell carcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical study, an ALK S1206Y secondary mutation in the context of an ALK fusion was associated with resistance to Xalkori (crizotinib) in a patient with non-small cell lung cancer (PMID: 22277784).	22277784
ALK T1151dup	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK T1151dup in an in vitro assay (PMID: 34158340).	34158340
ALK fusion ALK T1151dup	lung non-small cell carcinoma	no benefit	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, Zykadia (ceritinib) treatment did not result in disease control in a patient with non-small cell lung cancer and uterine metastasis harboring an ALK fusion and ALK T1151dup (reported as ALK 1151Tins) whose disease progressed after prior Xalkori (crizotinib) and Alecensa (alectinib) treatments (PMID: 34184417).	34184417
ALK fusion ALK T1151dup	lung non-small cell carcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in shrinkage of the pulmonary and uterine lesions in a patient with non-small cell lung cancer and uterine metastasis harboring an ALK fusion and ALK T1151dup (reported as ALK 1151Tins), and the patient remained recurrence-free over 1 year of treatment (PMID: 34184417).	34184417
EML4 - ALK ALK T1151dup	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK T1151dup in the context of EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK T1151dup	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK T1151dup in culture (PMID: 35421578).	35421578
EML4 - ALK ALK T1151dup	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK T1151dup (referred to as 1151insT) in culture and in xenograft models (PMID: 24887559).	24887559
EML4 - ALK ALK T1151dup	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK T1151dup in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK T1151dup	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK T1151dup in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784).	22277784
EML4 - ALK ALK T1151dup	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK T1151dup in culture (PMID: 35421578).	35421578
EML4 - ALK ALK T1151dup	Advanced Solid Tumor	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK and ALK T1151dup (reported as T1151insT) in culture (PMID: 39269178).	39269178
ALK G1202R	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Augtyro (repotrectinib) inhibited ALK G1202R and suppressed tumor growth in cell line xenograft models with ALK G1202R (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132).	detail...
ALK G1202R	Advanced Solid Tumor	predicted - sensitive	Conteltinib	Preclinical - Biochemical	Actionable	In a preclinical study, Conteltinib (CT-707) inhibited ALK G1202R activity in an in vitro assay (PMID: 36424628).	36424628
ALK G1202R	Advanced Solid Tumor	predicted - sensitive	APG-2449	Preclinical - Biochemical	Actionable	In a preclinical study, APG-2449 inhibited the kinase activity of ALK G1202R in culture (PMID: 35820889).	35820889
EML4 - ALK ALK G1202R	lung squamous cell carcinoma	predicted - resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1202R was identified in the post-progression biopsy of a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK, who previously responded to Alunbrig (brigatinib) treatment (PMID: 34376997).	34376997
EML4 - ALK ALK G1202R	lung adenocarcinoma	conflicting	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK, with acquired ALK G1202R and ALK E1154K in tumor biopsies, and ALK G1202R and ALK I1268V in ctDNA, experienced disease progression after 2.5 months of Alunbrig (brigatinib) treatment, and only increased allelic frequency of ALK G1202R was detected at disease progression (PMID: 31585938).	31585938
EML4 - ALK ALK G1202R	lung adenocarcinoma	conflicting	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response and 30 months of progression-free survival in a lung adenocarcinoma patient harboring EML4-ALK and de novo ALK G1202R (PMID: 35235872).	35235872
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853).	27780853
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1202R in culture (PMID: 35421578).	35421578
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Alunbrig (brigatinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to ASP3026 in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1202R	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK, who had developed resistance to Xalkori (crizotinib), was found to harbor ALK G1202R following treatment with Alecensa (alectinib) (PMID: 24736079).	24736079
EML4 - ALK ALK G1202R	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1202R was identified in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) after the disease progressed on Alecensa (alectinib) treatment (PMID: 35328235).	35328235
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) did not effectively inhibit growth of transformed cells expressing EML4-ALK with ALK G1202R in culture, and did not inhibit tumor growth in xenograft models (PMID: 24887559).	24887559
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Alecensa (alectinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784).	22277784
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	lung non-small cell carcinoma	resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who acquired the secondary drug resistance mutation, ALK S1206Y, when treated with Xalkori (crizotinib) was subsequently treated with Zykadia (ceritinib), developed drug resistance, and was then found to have lost the ALK S1206Y mutation, but gained ALK G1202R (PMID: 24675041).	24675041
EML4 - ALK ALK G1202R	lung non-small cell carcinoma	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were insensitive to Zykadia (ceritinib) in culture (PMID: 24675041).	24675041
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Zykadia (ceritinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	sarcoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with metastatic non-myofibroblastic sarcoma harboring EML4-ALK (e2:e20) and ALK I1171N experienced progressive disease on treatment with Lorbrena (lorlatinib) and was found to have lost ALK I1171N and acquired ALK G1202R (PMID: 39188081).	39188081
EML4 - ALK ALK G1202R	lung cancer	conflicting	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis in transformed cells over expressing ALK G1202R in the context of EML4-ALK in culture and in cell line xenograft models (PMID: 26144315).	26144315
EML4 - ALK ALK G1202R	lung cancer	conflicting	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1202R	lung squamous cell carcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, third-line Lorbrena (lorlatinib) treatment resulted in a progression-free survival of 7 months in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK and ALK G1202R (PMID: 34376997).	34376997
EML4 - ALK ALK G1202R	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with lung adenocarcinoma harboring EML4-ALK (e6a:e20) and ALK G1202R (PMID: 35328235).	35328235
EML4 - ALK ALK G1202R	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a partial response with a progression-free survival of 21.2 months, overall survival of 34.0 months, and a duration of treatment of 24.2 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) with ALK G1202R (PMID: 39500140).	39500140
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited tumor growth of a cell line xenograft model expressing EML4-ALK with ALK G1202R (PMID: 35820889).	35820889
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment inhibited tumor growth in a mouse cell line xenograft model expressing EML4-ALK and ALK G1202R (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202R demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK G1202R	Advanced Solid Tumor	conflicting	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, a cell line expressing EML4-ALK with ALK G1202R was resistant to Ensartinib (X-396) in culture (PMID: 31446141).	31446141
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to Ensartinib (X-396) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to Rozlytrek (entrectinib) in culture (PMID: 26939704).	26939704
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Xospata (gilteritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1202R	Advanced Solid Tumor	resistant	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to Xospata (gilteritinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK G1202R	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Augtyro (repotrectinib) inhibited Alk activity and proliferation of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 30093503).	30093503
EML4 - ALK ALK G1202R	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK G1202R in culture (PMID: 36201110).	36201110
EML4 - ALK ALK G1202R	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1202R in culture (PMID: 35421578).	35421578
EML4 - ALK ALK G1202R	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell line xenograft	Actionable	In a preclinical study, TPX-0131 inhibited Alk autophosphorylation and proliferation of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture and resulted in complete tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK G1202R in culture (PMID: 36201110).	36201110
EML4 - ALK ALK G1202R	lung non-small cell carcinoma	predicted - sensitive	Lorlatinib + PF-07284892	Case Reports/Case Series	Actionable	In a clinical case study, the combination of PF-07284892 and Lorbrena (lorlatinib) resulted in a partial response with a 50% tumor reduction after 6 weeks in a patient with non-small cell lung cancer harboring EML4-ALK and ALK G1202R, and the patient remained on the combination for 4.5 months (PMID: 37269335; NCT04800822).	37269335
EML4 - ALK ALK G1202R	lung non-small cell carcinoma	predicted - sensitive	NVL-655	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, NVL-655 inhibited Alk signaling and growth in patient-derived non-small cell lung cancer cell lines harboring EML4-ALK and ALK G1202R in culture and decreased brain tumor growth and improved survival in a patient-derived intracranial xenograft model (PMID: 39269178).	39269178
EML4 - ALK ALK G1202R	Advanced Solid Tumor	predicted - sensitive	NVL-655	Preclinical	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK and ALK G1202R in culture and inhibited tumor growth in a transplant model (PMID: 39269178).	39269178
EML4 - ALK ALK G1202R	Advanced Solid Tumor	sensitive	XMU-MP-5	Preclinical - Cell line xenograft	Actionable	In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1202R in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34845836).	34845836
EML4 - ALK ALK G1202R	lung non-small cell carcinoma	sensitive	HJC0152	Preclinical - Cell culture	Actionable	In a preclinical study, HJC0152 treatment decreased Stat signaling, migration, and invasion in a non-small cell lung cancer cell line expressing EML4-ALK and ALK G1202R in culture (PMID: 35085771).	35085771
EML4 - ALK ALK G1202R	lung non-small cell carcinoma	sensitive	Ceritinib + HJC0152	Preclinical - Cell culture	Actionable	In a preclinical study, HJC0152 and Zykadia (ceritinib) combination treatment increased apoptosis and decreased viability and colony formation in a non-small cell lung cancer cell line expressing EML4-ALK and ALK G1202R compared to either drug alone in culture (PMID: 35085771).	35085771
EML4 - ALK ALK G1202R	Advanced Solid Tumor	sensitive	APG-2449	Preclinical - Cell line xenograft	Actionable	In a preclinical study, APG-2449 inhibited tumor growth of a cell line xenograft model expressing EML4-ALK with ALK G1202R (PMID: 35820889).	35820889
ALK fusion ALK G1202R	lung non-small cell carcinoma	sensitive	Lorlatinib	Phase I	Actionable	In a Phase I trial, treatment with Lorlatinib (PF-06463922) demonstrated safety and resulted in durable responses in patients with ALK-positive non-small cell lung cancer, including patients harboring ALK G1202R (J Clin Oncol 34, 2016 (suppl; abstr 9009)).	detail...
ALK fusion ALK G1202R	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a partial response with a progression-free survival of 3.9 months, overall survival of 12.3 months, and a duration of treatment of 4.9 months in a patient with lung adenocarcinoma harboring an ALK fusion with ALK G1202R (PMID: 39500140).	39500140
ALK fusion ALK G1202R	lung non-small cell carcinoma	predicted - sensitive	NVL-655	Phase I	Actionable	In a Phase I trial (ALKOVE-1), NVL-655 treatment demonstrated activity in patients with ALK-positive non-small cell lung cancer (including patients with ALK fusion with or without secondary ALK mutations), with a response rate of 76% (22/29), a median duration of response (DOR) of 14.4 mo, DOR greater than 6 months in 88% of patients, and a response rate of 83% (10/12) at the RP2D dose of 150mg in patients harboring an ALK fusion with ALK G1202R (Ann Oncol (2024) 35 (suppl_2): S802-S803; NCT05384626).	detail...
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1198F and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F and G1202R in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment did not inhibit proliferation of transformed cells expressing ALK G1202R and L1198F compound mutation in the context of EML4-ALK culture and resulted in only 30% tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorbrena (lorlatinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F and G1202R in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell line xenograft	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F and ALK G1202R compound mutation in the context of EML4-ALK in culture, and resulted in complete tumor growth regression in a cell line xenograft model (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R	Advanced Solid Tumor	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK, ALK G1202R, and ALK L1198F in culture (PMID: 39269178).	39269178
EML4 - ALK ALK F1174V ALK G1202R	lung non-small cell carcinoma	sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who was previously treated with Xalkori (crizotinib) and subsequently developed the resistance mutation, ALK G1269A, was treated with Zykadia (ceritinib), later progressed, and was found to have lost ALK G1269A, but gained ALK F1174V and ALK G1202R (PMID: 24675041).	24675041
ALK fusion ALK G1202R KIT amp	lung non-small cell carcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical study, an ALK G1202R secondary mutation as well as KIT amplification were identified in a patient with ALK fusion-positive non-small cell lung cancer with resistance to Xalkori (crizotinib) (PMID: 22277784).	22277784
ALK G1202R ALK pos	lung non-small cell carcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 33% (2/6, all partial responses) and stable disease in 50% (3/6) of patients with ALK-positive non-small cell lung cancer harboring ALK G1202R (PMID: 31628085; NCT0321569).	31628085
EML4 - ALK ALK E1154K ALK G1202R ALK I1268V	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response lasting 9.2 months in a patient with lung adenocarcinoma harboring EML4-ALK, at disease progression, ALK G1202R and ALK E1154K were identified in biopsies, while ALK G1202R and ALK I1268V were identified in ctDNA (PMID: 31585938).	31585938
EML4 - ALK ALK E1154K ALK G1202R ALK I1268V	lung adenocarcinoma	predicted - resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, Zykadia (ceritinib) treatment resulted rapid disease progression in a patient with lung adenocarcinoma harboring EML4-ALK, with acquired ALK G1202R and ALK E1154K in tumor biopsies, and ALK G1202R and ALK I1268V in ctDNA (PMID: 31585938).	31585938
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK C1156Y compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and C1156Y were resistant to Alecensa (alectinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK C1156Y compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and C1156Y were resistant to Xalkori (crizotinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and C1156Y compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and C1156Y compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and C1156Y were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and C1156Y were resistant to Xospata (gilteritinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK C1156Y and ALK G1202R compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK G1202R	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK G1202R and C1156Y in culture (PMID: 36201110).	36201110
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1269A and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK G1269A were resistant to Alecensa (alectinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK G1269A were resistant to Xalkori (crizotinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK G1269A	lung adenocarcinoma	predicted - sensitive	NVL-655	Case Reports/Case Series	Actionable	In a Phase I trial (ALKOVE-1), NVL-655 treatment resulted in a partial response with treatment ongoing for at least 5 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK, ALK G1202R, and ALK G1269A (PMID: 39269178; NCT05384626).	39269178
EML4 - ALK ALK G1202R ALK G1269A	Advanced Solid Tumor	predicted - sensitive	NVL-655	Preclinical	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK, ALK G1202R, and ALK G1269A in culture and induced tumor regression in a transplant model (PMID: 39269178).	39269178
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1269A, L1204V, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, G1269A, and L1204V compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1202R, ALK L1204V, and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1269A, L1198F, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, G1269A, and L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F, ALK G1202R, and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK V1180L ALK G1202R	large cell neuroendocrine carcinoma	predicted - resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK and acquired ALK V1180L and ALK G1202R mutations demonstrated further progressive disease 2 weeks after initiating Alunbrig (brigatinib) treatment (PMID: 34994612).	34994612
EML4 - ALK ALK V1180L ALK G1202R	large cell neuroendocrine carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK developed progressive disease after initial response to Alecensa (alectinib) treatment, post-progression circulating tumor DNA analysis identified the acquisition of ALK V1180L and ALK G1202R, together with TP53 G105V and MYCN E378fs (PMID: 34994612).	34994612
EML4 - ALK ALK V1180L ALK G1202R	large cell neuroendocrine carcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in clinical improvement and regression of lung lesions after 4 weeks of therapy in a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK and acquired ALK V1180L and ALK G1202R mutations; however, new bone lesions and progression of the brain mass was seen, and significant progressive disease developed after 3 months (PMID: 34994612).	34994612
ALK L1198F ALK G1202R	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK G1202R and L1198F compound mutation in an in vitro assay (PMID: 34158340).	34158340
EML4 - ALK ALK G1202R ALK S1206F	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Alunbrig (brigatinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK G1202R ALK S1206F	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Alecensa (alectinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK G1202R ALK S1206F	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Xalkori (crizotinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK G1202R ALK S1206F	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Zykadia (ceritinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK G1202R ALK S1206F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Alunbrig (brigatinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Alecensa (alectinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Xalkori (crizotinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, S1206F, and G1269A were resistant to Zykadia (ceritinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK T1151K ALK G1202R ALK S1206F	lung adenocarcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK S1206F and ALK T1151K were identified in a patient with lung adenocarcinoma harboring EML4-ALK (e6a:e20) and ALK G1202R after the disease progressed on Lorbrena (lorlatinib) treatment (PMID: 35328235).	35328235
ALK fusion ALK G1202R ALK L1204V ALK G1269A	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1204V and ALK G1269A were identified as acquired mutations in a non-small cell lung cancer patient harboring an ALK fusion with ALK G1202R who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063).	35726063
ALK fusion ALK G1202R ALK S1206F ALK G1269A	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK S1206F and ALK G1269A were identified as acquired mutations in a non-small cell lung cancer patient harboring an ALK fusion with ALK G1202R who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063).	35726063
EML4 - ALK ALK E1129V ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and E1129V were resistant to Alecensa (alectinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK E1129V ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and E1129V were resistant to Xalkori (crizotinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK E1129V ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and E1129V were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK E1129V ALK G1202R	Advanced Solid Tumor	resistant	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and E1129V were resistant to Xospata (gilteritinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK E1129V ALK G1202R	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK G1202R and E1129V in culture (PMID: 36201110).	36201110
EML4 - ALK ALK F1174C ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to Alecensa (alectinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK F1174C ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to Xalkori (crizotinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK F1174C ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK F1174C ALK G1202R	Advanced Solid Tumor	resistant	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to Xospata (gilteritinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK F1174C ALK G1202R	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to TPX-0131 in culture (PMID: 36201110).	36201110
EML4 - ALK ALK F1174C ALK G1202R	lung adenocarcinoma	sensitive	NVL-655	Case Reports/Case Series	Actionable	In a Phase I trial (ALKOVE-1), NVL-655 treatment resulted in a partial response with treatment ongoing for at least 9 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK with ALK G1202R and F1174C in cis (PMID: 39269178; NCT05384626).	39269178
EML4 - ALK ALK F1174I ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Alecensa (alectinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK F1174I ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Xalkori (crizotinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK F1174I ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK F1174I ALK G1202R	Advanced Solid Tumor	resistant	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Xospata (gilteritinib) in culture (PMID: 36201110).	36201110
EML4 - ALK ALK F1174I ALK G1202R	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to TPX-0131 in culture (PMID: 36201110).	36201110
EML4 - ALK ALK T1151M ALK G1202R	lung non-small cell carcinoma	resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response lasting 10 months in a patient with non-small cell lung cancer harboring EML4-ALK with ALK G1202R and ALK T1151M (PMID: 39363320; NCT02517892).	39363320
EML4 - ALK ALK T1151M ALK G1202R	lung non-small cell carcinoma	resistant	Brigatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK, ALK G1202R, and ALK T1151M was resistant to Alunbrig (brigatinib) treatment in culture (PMID: 39269178).	39269178
EML4 - ALK ALK T1151M ALK G1202R	lung non-small cell carcinoma	resistant	Alectinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK, ALK G1202R, and ALK T1151M was resistant to Alecensa (alectinib) treatment in culture (PMID: 39269178).	39269178
EML4 - ALK ALK T1151M ALK G1202R	lung non-small cell carcinoma	resistant	Crizotinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK, ALK G1202R, and ALK T1151M was resistant to Xalkori (crizotinib) treatment in culture (PMID: 39269178).	39269178
EML4 - ALK ALK T1151M ALK G1202R	lung non-small cell carcinoma	resistant	Ceritinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK, ALK G1202R, and ALK T1151M was resistant to Zykadia (ceritinib) treatment in culture (PMID: 39269178).	39269178
EML4 - ALK ALK T1151M ALK G1202R	lung non-small cell carcinoma	resistant	Lorlatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK, ALK G1202R, and ALK T1151M was resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 39269178).	39269178
EML4 - ALK ALK T1151M ALK G1202R	lung non-small cell carcinoma	sensitive	NVL-655	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, NVL-655 inhibited Alk signaling and viability of a patient-derived non-small cell lung cancer cell line expressing EML4-ALK, ALK G1202R, and ALK T1151M in culture and induced tumor regression in a patient-derived xenograft (PDX) model (PMID: 39269178).	39269178
EML4 - ALK ALK T1151M ALK G1202R	Advanced Solid Tumor	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK, ALK G1202R, and ALK T1151M in culture (PMID: 39269178).	39269178
ALK G1202R ALK D1276_R1279delinsE	neuroblastoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a neuroblastoma patient harboring ALK D1276_R1279delinsE developed progressive disease on treatment with Xalkori (crizotinib) and was found to have acquired ALK G1202R via circulating tumor DNA (PMID: 37147298).	37147298
ALK G1202R ALK D1276_R1279delinsE	neuroblastoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a complete metabolic response and a partial anatomic response in a neuroblastoma patient harboring ALK D1276_R1279delinsE and G1202R, who remained on the treatment for over 27 cycles (PMID: 37147298; NCT03107988).	37147298
ALK amp	neuroblastoma	no benefit	Crizotinib	Case Reports/Case Series	Actionable	In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, although both patients harboring ALK amplification had disease progression after only 1 cycle of treatment (PMID: 33568345; NCT00939770).	33568345
ALK amp	neuroblastoma	no benefit	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) was less efficient than Lorlatinib (PF-06463922) to induced growth inhibition in ALK-amplified neuroblastoma cells in culture (PMID: 26554404).	26554404
ALK amp	neuroblastoma	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited growth of ALK-amplified neuroblastoma cells in culture (PMID: 26554404).	26554404
ALK amp	neuroblastoma	sensitive	Lorlatinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a panel of ALK-amplified neuroblastoma cell lines in culture, and inhibited tumor growth in a patient-derived xenograft (PDX) model (PMID: 36602782).	36602782
ALK amp	lung non-small cell carcinoma	no benefit	Belizatinib	Phase I	Actionable	In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488).	31217479
ALK amp	neuroblastoma	predicted - sensitive	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ensartinib (X-396) treatment resulted in inhibition of cell proliferation in a neuroblastoma cell line harboring ALK amplification in culture (PMID: 34482287).	34482287
ALK amp	neuroblastoma	sensitive	CEP-28122	Preclinical - Cell culture	Actionable	In a preclinical study, CEP-28122 inhibited growth of ALK-amplified neuroblastoma cells in culture (PMID: 22203728).	22203728
ALK amp	neuroblastoma	predicted - sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) treatment resulted in inhibition of cell proliferation in a neuroblastoma cell line harboring ALK amplification in culture (PMID: 34482287).	34482287
ALK amp	neuroblastoma	predicted - sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NUV-655 inhibited proliferation of neuroblastoma cell lines with ALK amplification in culture (Cancer Res (2022) 82 (12_Supplement): 3337).	detail...
ALK amp	neuroblastoma	no benefit	Cyclophosphamide + Doxorubicin + Lorlatinib + Vincristine Sulfate	Preclinical - Pdx	Actionable	In a preclinical study, addition of Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), and Oncovin (vincristine) to Lorbrena (lorlatinib) did not improve tumor growth inhibition in a patient-derived xenograft (PDX) model of neuroblastoma with ALK amplification and overexpression (PMID: 36602782).	36602782
ALK amp TP53 wild-type	neuroblastoma	sensitive	Ceritinib + CGM097	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of Zykadia (ceritinib) and CGM097 inhibited Alk signaling and resulted in synergistic inhibition of proliferation in a TP53 wild-type, ALK-amplified neuroblastoma cell line in culture and induced tumor regression in a cell line xenograft model (PMID: 28425916).	28425916
ALK amp TP53 wild-type	neuroblastoma	sensitive	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in neuroblastoma cell lines harboring Alk amplification and functional TP53, resulting in growth inhibition in culture (PMID: 26438783).	26438783
ALK amp TP53 wild-type	neuroblastoma	sensitive	Idasanutlin + Lorlatinib	Preclinical - Pdx	Actionable	In a preclinical study, combination treatment with Lorbrena (lorlatinib) and Idasanutlin (RG7388) resulted in an additive effect on tumor growth inhibition with complete remission in a patient-derived xenograft (PDX) model of TP53 wild-type neuroblastoma with ALK amplification and overexpression (PMID: 36602782).	36602782
ALK amp TP53 wild-type	neuroblastoma	sensitive	Alectinib + Idasanutlin	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line with ALK amplification in culture (PMID: 36602782).	36602782
ALK F1174V ALK amp	neuroblastoma	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174V in culture (PMID: 29907598).	29907598
ALK F1174V ALK amp	neuroblastoma	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174V in culture (PMID: 29907598).	29907598
ALK F1174V ALK amp	neuroblastoma	sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) inhibited downstream signaling and proliferation, and induced apoptosis in a neuroblastoma cell line harboring ALK F1174V and ALK amplification in culture (PMID: 31852910).	31852910
ALK amp ALK pos	lung non-small cell carcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 56% (5/9, all partial responses) and stable disease in 44% (4/9) of patients with ALK-positive non-small cell lung cancer with ALK amplification (PMID: 31628085; NCT0321569).	31628085
ALK F1174V ALK amp TP53 wild-type	neuroblastoma	sensitive	Idasanutlin + TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, TAE684 and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK F1174V and ALK amplification in culture (PMID: 36602782).	36602782
ALK F1174V ALK amp TP53 wild-type	neuroblastoma	sensitive	Alectinib + Idasanutlin	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth and induced apoptosis in a TP53 wild-type neuroblastoma cell line harboring ALK F1174V and ALK amplification in culture (PMID: 36602782).	36602782
ALK del exon2 ALK del exon3 ALK amp	neuroblastoma	sensitive	Ceritinib + Ribociclib	Preclinical - Cell culture	Actionable	In a preclinical study, the combination of Zykadia (ceritinib) and Kisqali (ribociclib) inhibited proliferation in a neuroblastoma cell line harboring a deletion of ALK exons 2 and 3 and ALK amplification in culture (PMID: 27986745).	27986745
ALK del exon2-3 ALK amp	neuroblastoma	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of an ALK-amplified neuroblastoma cell line harboring a deletion of ALK exons 2-3 in culture (PMID: 39269178).	39269178
ALK positive	lung non-small cell carcinoma	no benefit	Brigatinib	Phase II	Actionable	In a Phase II trial (ALTA-2), Alunbrig (brigatinib) therapy demonstrated limited efficacy in ALK-positive advanced non-small cell lung cancer patients who previously progressed on Alecensa (alectinib) or Zykadia (ceritinib) therapy, with an objective response rate (ORR) of 26.2% (27/103, 1 complete (CR) and 26 partial responses), duration of response of 6.3 mo, median progression-free survival of 3.8 mo, and intracranial ORR of 15% (8/55, 1 CR) in patients with CNS metastases (PMID: 36096442; NCT05421936).	36096442
ALK positive	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response in a pregnant patient with ALK-positive metastatic lung adenocarcinoma, with no developmental effects observed during pregnancy or the first 9 months of the infant’s life (PMID: 37087822).	37087822
ALK positive	inflammatory myofibroblastic tumor	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in partial remission before treatment discontinuation and complete remission following restart of treatment in a 7-year-old pediatric patient with ALK-positive recurrent, metastatic inflammatory myofibroblastic tumor (PMID: 36515740).	36515740
ALK positive	neuroblastoma	predicted - sensitive	Ceritinib	Phase I	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 20% (6/30; 6 partial response), a disease control rate of 53% (16/30), and a median progression-free survival of 2.4 months in pediatric patients with ALK-positive neuroblastoma (PMID: 34780709; NCT01742286).	34780709
ALK positive	Advanced Solid Tumor	predicted - sensitive	Ceritinib	Phase I	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 14% (1/7), a disease control rate of 43% (3/7), and a progression-free survival of 1.9 months in pediatric patients with ALK-positive advanced solid tumors other than neuroblastoma, anaplastic large cell lymphoma, or inflammatory myofibroblastic tumor (PMID: 34780709; NCT01742286).	34780709
ALK positive	lung non-small cell carcinoma	sensitive	Ensartinib	Phase II	Actionable	In a Phase II trial, Ensartinib (X-396) treatment resulted in an objective response in 52% (76/147; all partial responses), and disease control in 93% (137/147) of patients with crizotinib-refractory ALK-positive non-small cell lung cancer, and a median progression-free survival of 9.6 mo., and of the 97 patients with brain metastases, 41% (40) demonstrated a partial response, and of those, 28 (70%) had an intracranial response and 39 (98%) had intracranial disease control (PMID: 31628085; NCT03215693).	31628085
ALK positive	neuroblastoma	sensitive	Entrectinib	Case Reports/Case Series	Actionable	In a Phase I trial, Rozlytrek (entrectinib) treatment resulted in partial response in a patient with ALK-positive neuroblastoma (J Clin Oncol 32:5s, 2014 (suppl; abstr 2502)).	detail...
ALK positive	lung non-small cell carcinoma	sensitive	Entrectinib	Case Reports/Case Series	Actionable	In a Phase I trial, Rozlytrek (entrectinib) treatment resulted in stable disease in a patient with ALK-positive non-small cell lung carcinoma (J Clin Oncol 32:5s, 2014 (suppl; abstr 2502)).	detail...
ALK C1156Y ALK pos	lung non-small cell carcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 71% (5/7, all partial responses) and stable disease in 29% (2/7) of patients with ALK-positive non-small cell lung cancer harboring ALK C1156Y (PMID: 31628085; NCT0321569).	31628085
ALK I1171T ALK pos	lung non-small cell carcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 50% (2/4) of patients with ALK-positive non-small cell lung cancer harboring ALK I1171T (n=3) or I1171S (n=1) (PMID: 31628085; NCT0321569).	31628085
ALK I1171S ALK pos	lung non-small cell carcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 50% (2/4) of patients with ALK-positive non-small cell lung cancer harboring ALK I1171T (n=3) or I1171S (n=1) (PMID: 31628085; NCT0321569).	31628085
ALK F1174V ALK pos	lung non-small cell carcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 71% (5/7, all partial responses) of patients with ALK-positive non-small cell lung cancer harboring ALK F1174L (n=5) or ALK F1174V (n=1) (PMID: 31628085; NCT0321569).	31628085
ALK L1152R ALK pos	lung non-small cell carcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 25% (1/4) of patients with ALK-positive non-small cell lung cancer harboring ALK L1152R (n=3) or L1152V (n=1) (PMID: 31628085; NCT0321569).	31628085
ALK L1152V ALK pos	lung non-small cell carcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 25% (1/4) of patients with ALK-positive non-small cell lung cancer harboring ALK L1152R (n=3) or L1152V (n=1) (PMID: 31628085; NCT0321569).	31628085
ALK L1152R	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK L1152R in an in vitro assay (PMID: 34158340).	34158340
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 35421578).	35421578
EML4 - ALK ALK L1152R	Advanced Solid Tumor	resistant	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152R demonstrated resistance to ASP3026 in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of a cell line expressing EML4-ALK with ALK L1152R in culture (PMID: 31446141).	31446141
EML4 - ALK ALK L1152R	lung non-small cell carcinoma	resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a brief response to Xalkori (crizotinib) treatment, but after 3 months showed tumor progression, and was found to harbor the secondary resistance mutation, ALK L1152R (PMID: 21791641).	21791641
EML4 - ALK ALK L1152R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1152R in the context of EML4-ALK demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 21791641).	21791641
EML4 - ALK ALK L1152R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152R demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1152R	lung cancer	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, lung cancer cells expressing ALK L1152R in the context of EML4-ALK demonstrated resistance to Zykadia (ceritinib) treatment in culture (PMID: 31925410).	31925410
EML4 - ALK ALK L1152R	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1152R in the context of EML4-ALK demonstrated reduced sensitivity to Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK L1152R	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152R demonstrated resistance to Zykadia (ceritinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 26144315).	26144315
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK L1152R in culture (PMID: 31446141).	31446141
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK L1152R in culture (PMID: 31446141).	31446141
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 35421578).	35421578
EML4 - ALK ALK L1152R	Advanced Solid Tumor	sensitive	TQ-B3139	Preclinical - Cell culture	Actionable	In a preclinical study, TQ-B3139 (CT-117) inhibited proliferation of a cells expressing EML4-ALK with ALK L1152R in culture (PMID: 30210922).	30210922
ALK C1156Y	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Biochemical	Actionable	In a preclinical study, ALK C1156Y was sensitive to Alecensa (alectinib) in an in vitro enzyme assay (PMID: 21575866).	21575866
ALK C1156Y	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK C1156Y in an in vitro assay (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 25727400).	25727400
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640).	33627640
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, ASP3026 inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 25727400).	25727400
EML4 - ALK ALK C1156Y	lung non-small cell carcinoma	no benefit	Luminespib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer with an ALK C1156Y secondary Xalkori (crizotinib) resistance mutation did not respond to Luminespib (AUY922) therapy (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 24887559).	24887559
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 25727400).	25727400
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed human cells expressing EML4-ALK with ALK C1156Y were sensitive to Alecensa (alectinib) in culture (PMID: 21575866).	21575866
EML4 - ALK ALK C1156Y	lung non-small cell carcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer developed resistance to Xalkori (crizotinib) with the emergence of ALK C1156Y, a secondary resistance mutation (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK ALK C1156Y were insensitive to Xalkori (crizotinib) as demonstrated by lack of growth inhibition and lack of kinase inhibition in culture (PMID: 21613408).	21613408
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y demonstrated moderate resistance to Xalkori (crizotinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	lung non-small cell carcinoma	conflicting	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer with a secondary Xalkori (crizotinib) resistance mutation C1156Y, did not respond to Zykadia (ceritinib) therapy (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	lung non-small cell carcinoma	conflicting	Ceritinib	Case Reports/Case Series	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment resulted in a partial response in a patient with non-small cell lung cancer harboring EML4-ALK (e18:e20) and ALK C1156Y (PMID: 34890832; NCT01283516).	34890832
EML4 - ALK ALK C1156Y	lung non-small cell carcinoma	conflicting	Ceritinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Zykadia (ceritinib) demonstrated tumor growth inhibition in xenograft models of a human non-small cell lung cancer cell line harboring EML4-ALK with ALK C1156Y when compared to Xalkori (crizotinib) (PMID: 24675041).	24675041
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	predicted - sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed human cells expressing ALK C1156Y in the context of EML4-ALK demonstrated minimal sensitivity to Zykadia (ceritinib) in culture (PMID: 24675041).	24675041
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	predicted - sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	predicted - sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 25727400).	25727400
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	predicted - sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640).	33627640
EML4 - ALK ALK C1156Y	lung non-small cell carcinoma	sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, a patient with EML4-ALK positive non-small cell lung cancer with a secondary Xalkori (crizotinib) resistance mutation ALK C1156Y, was treated with Lorlatinib (PF-06463922) and displayed a 41% reduction in tumor growth after 5 weeks of treatment (PMID: 26698910; NCT01970865).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK C1156Y in culture (PMID: 31446141).	31446141
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640).	33627640
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorlatinib (PF-06463922) inhibited growth and ALK phosphorylation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Ensartinib	Preclinical	Actionable	In a preclinical study, Ensartinib (X-396) inhibited growth and Alk phosphorylation in cells expressing the Xalkori (crizotinib) resistance mutation, EML4-ALK C1156Y (PMID: 21613408).	21613408
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK C1156Y in culture (PMID: 31446141).	31446141
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640).	33627640
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y were sensitive to Rozlytrek (entrectinib), resulting in anti-proliferative activity (PMID: 26939704).	26939704
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640).	33627640
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) inhibited growth of transformed cells expressing ALK C1156Y in the context of EML4-ALK in culture (PMID: 35421578).	35421578
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK and ALK C1156Y in culture (PMID: 39269178).	39269178
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	XMU-MP-5	Preclinical - Cell culture	Actionable	In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 34845836).	34845836
EML4 - ALK ALK C1156Y	Advanced Solid Tumor	sensitive	TQ-B3139	Preclinical - Cell line xenograft	Actionable	In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of cells expressing EML4-ALK with ALK C1156Y in culture and inhibited tumor growth in a cell line xenograft model (PMID: 30210922).	30210922
EML4 - ALK ALK C1156Y	lung non-small cell carcinoma	sensitive	Afatinib + Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of Gilotrif (afatinib) and Lorbrena (lorlatinib) further inhibited viability of a patient-derived non-small cell lung cancer cell line harboring EML4-ALK (e6:e19) with ALK C1156Y compared to Lorbrena (lorlatinib) alone in culture (PMID: 37748191).	37748191
ALK fusion ALK C1156Y	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a retrospective analysis, Alecensa (alectinib) treatment resulted in a partial response with a progression-free survival of 6.3 months, overall survival of 8.2 months, and a duration of treatment of 8.1 months in a patient with lung adenocarcinoma harboring an ALK fusion with ALK C1156Y (PMID: 39500140).	39500140
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 35726063).	35726063
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and ALK L1198F in the context of EML4-ALK were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y ALK L1198F	lung non-small cell carcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with EML4-ALK positive non-small lung cancer initially responded to Xalkori (crizotinib) but developed resistance with the emergence of a secondary ALK mutation C1156Y, and subsequently redeveloped sensitivity to Xalkori (crizotinib) upon the emergence of a second ALK mutation, L1198F arising from resistance to Lorlatinib (PF-06463922) (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 35726063).	35726063
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to Zykadia (ceritinib) in culture (PMID: 35726063).	35726063
EML4 - ALK ALK C1156Y ALK L1198F	lung non-small cell carcinoma	resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, a patient with EML4-ALK positive non-small lung cancer with a secondary Xalkori (critzotinib) resistance mutation C1156Y, responded to Lorlatinib (PF-06463922) but subsequently developed resistance upon the emergence of a second ALK mutation, L1198F (PMID: 26698910; NCT01970865).	26698910
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK C1156Y ALK L1198F	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK C1156Y and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK C1156Y ALK I1171T	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK C1156Y ALK F1174C	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK C1156Y ALK F1174I	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK F1174I was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK C1156Y ALK F1174V	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK C1156Y ALK D1203N	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK D1203N was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK C1156Y ALK L1256F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK C1156Y ALK G1269A	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK in culture (PMID: 31585938).	31585938
EML4 - ALK ALK C1156Y ALK G1269A	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) in culture (PMID: 31585938).	31585938
EML4 - ALK ALK C1156Y ALK G1269A	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 31585938).	31585938
EML4 - ALK ALK C1156Y ALK G1269A	lung adenocarcinoma	unknown	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 6.9 months of therapy in a patient with lung adenocarcinoma harboring EML4-ALK, ALK C1156Y and ALK G1269A were identified in biopsies at disease progression, however, cells derived from the patient-derived xenograft (PDX) model of the patient and transformed cells expressing the compound mutation demonstrated sensitivity to Lorbrena (lorlatinib) in culture (PMID: 31585938).	31585938
EML4 - ALK ALK C1156Y ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK C1156Y ALK G1269A	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK were resistant to Rozlytrek (entrectinib) in culture (PMID: 31585938).	31585938
EML4 - ALK ALK C1156Y ALK G1269A	lung adenocarcinoma	sensitive	Lorlatinib + Saracatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, Saracatinib (AZD0530) and Lorbrena (lorlatinib) synergistically inhibited viability of cells derived from the tumor from a patient with lung adenocarcinoma harboring EML4-ALK and acquired ALK C1156Y and G1269A compound mutation in culture (PMID: 31585938).	31585938
ALK C1156Y ALK L1198F	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK C1156Y and ALK L1198F compound mutation in an in vitro assay (PMID: 34158340).	34158340
ALK fusion ALK C1156Y ALK L1198F	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1198F was identified as an acquired mutation in a non-small cell lung cancer patient harboring an ALK fusion with ALK C1156Y who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063).	35726063
EML4 - ALK ALK C1156Y ALK I1171T ALK L1198F	lung non-small cell carcinoma	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited viability of a patient-derived non-small cell lung cancer cell line harboring EML4-ALK (e6:e19) with ALK C1156Y, I1171T, and L1198F in culture (PMID: 37748191).	37748191
EML4 - ALK ALK C1156Y ALK I1171T ALK L1198F	lung non-small cell carcinoma	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK (e6:e19) with ALK C1156Y, I1171T, and L1198F was resistant to Lorbrena (lorlatinib) in culture (PMID: 37748191).	37748191
EML4 - ALK ALK C1156Y ALK I1171T ALK L1198F	lung non-small cell carcinoma	sensitive	Afatinib + Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of Gilotrif (afatinib) and Xalkori (crizotinib) further inhibited viability of a patient-derived non-small cell lung cancer cell line harboring EML4-ALK (e6:e19) with ALK C1156Y, I1171T, and L1198F compared to Xalkori (crizotinib) alone in culture (PMID: 37748191).	37748191
ALK fusion	lung non-small cell carcinoma	sensitive	Brigatinib	Phase Ib/II	Actionable	In a phase I/II clinical trial, Alunbrig (brigatinib) was determined to be safe and efficacious in patients with advanced, ALK-fusion positive NSCLC (PMID: 24091716).	24091716
ALK fusion	lung non-small cell carcinoma	sensitive	Brigatinib	FDA approved - Has Companion Diagnostic	Actionable	In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged (fusion) non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573).	28475456 detail...
ALK fusion	lung non-small cell carcinoma	sensitive	Brigatinib	FDA approved - Has Companion Diagnostic	Actionable	In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501).	detail... detail... detail...
ALK fusion	lung adenocarcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in a significant reduction of brain metastases in a patient with lung adenocarcinoma harboring an ALK fusion (PMID: 38158887).	38158887
ALK fusion	Erdheim-Chester disease	sensitive	Brigatinib	Guideline	Actionable	Alunbrig (brigatinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org).	detail...
ALK fusion	lung non-small cell carcinoma	sensitive	Alectinib	Phase II	Actionable	In a Phase II trial, treatment with Alecensa (alectinib) resulted in a 49% (60/122) overall response rate in non-small cell lung cancer patients positive for an ALK fusion who had previously progressed on Xalkori (crizotinib) therapy (J Clin Oncol 33, 2015 (suppl; abstr 8008))	detail...
ALK fusion	lung non-small cell carcinoma	sensitive	Alectinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in non-small cell lung cancer patients harboring ALK rearrangements (PMID: 28586279; NCT02075840).	detail... 28586279 detail...
ALK fusion	lung non-small cell carcinoma	sensitive	Alectinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase III trial supporting FDA approval (ALINA), adjuvant Alecensa (alectinib) treatment improved 2-year disease-free survival rate (93.8% vs 63.0%, HR 0.24, p<0.001) compared to chemotherapy in patients with resected non-small cell lung cancer harboring ALK fusion, and was associated with CNS disease-free survival benefit (HR 0.22) (PMID: 38598794; NCT03456076).	detail... 38598794 detail...
ALK fusion	lung non-small cell carcinoma	sensitive	Alectinib	Phase III	Actionable	In a Phase III trial, treatment with Alecensa (alectinib) resulted in improved progression-free survival compared to treatment with Xalkori (crizotinib) (HR=0.34) in ALK-positive non-small cell lung cancer patients (J Clin Oncol 34, 2016 (suppl; abstr 9008)).	detail...
ALK fusion	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in shrinkage of brain metastases after 6 months in a patient with concomitant ALK fusion-positive lung adenocarcinoma and ERBB2 (HER2)-mutant, hormone receptor-negative invasive ductal carcinoma of the breast (PMID: 37113357).	37113357
ALK fusion	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in shrinkage of the brain and spinal cord metastases in a patient with ALK-positive lung adenocarcinoma, who had been previously treated with Xalkori (crizotinib) (PMID: 35373538).	35373538
ALK fusion	Erdheim-Chester disease	sensitive	Alectinib	Guideline	Actionable	Alecensa (alectinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org).	detail...
ALK fusion	renal cell carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a complete radiological response ongoing for at least 12 months in a patient with metastatic renal cell carcinoma harboring an ALK fusion (PMID: 39205743).	39205743
ALK fusion	Advanced Solid Tumor	predicted - sensitive	Alectinib	Phase Ib/II	Actionable	In a Phase I/II trial, Alecensa (alectinib) treatment resulted in 1 complete response, 3 partial responses, and 2 stable diseases in 7 evaluable pediatric patients with advanced solid tumors harboring ALK fusions with TPM3, CLTC, PLEKHA7, DCTN1, or HNRNPA3 (Cancer Res (2024) 84 (7_Supplement): CT039; NCT04774718).	detail...
ALK fusion	lung non-small cell carcinoma	sensitive	Crizotinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140).	25470694 detail... detail...
ALK fusion	lung adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in reduction of the lung tumors in a patient with metastatic ALK-positive lung adenocarcinoma, however, there was development of new brain metastases (PMID: 35373538).	35373538
ALK fusion	Erdheim-Chester disease	sensitive	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org).	detail...
ALK fusion	anaplastic large cell lymphoma	sensitive	Crizotinib	FDA approved	Actionable	In a Phase I/II trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate (ORR) of 83% (5/6, all complete responses (CR)) at the 165 mg dose, and an ORR of 90% (18/20, 16 CR) at the 280 mg dose, in pediatric patients 1 years of age or older and young adults with relapsed or refractory ALK-positive anaplastic large cell lymphoma (PMID: 28787259; NCT00939770).	28787259 detail...
ALK fusion	inflammatory myofibroblastic tumor	sensitive	Crizotinib	FDA approved	Actionable	In a Phase I/II trial (Study ADVL0912) that supported FDA approval, Xalkori (crizotinib) therapy was safe and resulted in an objective response rate of 86% (12/14, 5 complete responses, 7 partial responses) and stable disease in 14% (2/14) of pediatric patients with ALK-positive unresectable inflammatory myofibroblastic tumors, with a median duration of response of 1.63 years (PMID: 28787259; NCT00939770).	detail... 28787259
ALK fusion	inflammatory myofibroblastic tumor	sensitive	Crizotinib	FDA approved	Actionable	In a Phase Ib trial (PROFILE 1013) that supported FDA approval, treatment with Xalkori (crizotinib) resulted in an objective response rate of 66.7% (6/9, 1 complete response, 5 partial responses) and stable disease in 33.3% (3/9) of adult patients with advanced ALK-positive inflammatory myofibroblastic tumors, with a median duration of response of 74.1 weeks in (PMID: 29352732; NCT00939770).	29352732 detail...
ALK fusion	lung non-small cell carcinoma	sensitive	Ceritinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase I trial that supported FDA approval, Zykadia (ceritinib) resulted in a blinded independent review committee (BIRC)-assessed objective response rate of 44% (72/163) and a duration of response of 7.1 months in ALK-rearranged non-small cell lung cancer patients (PMID: 25754348; NCT01283516).	detail... detail... 25754348
ALK fusion	Erdheim-Chester disease	sensitive	Ceritinib	Guideline	Actionable	Zykadia (ceritinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org).	detail...
ALK fusion	lung non-small cell carcinoma	sensitive	Lorlatinib	Phase I	Actionable	In a Phase I trial, Lorlatinib (PF-06463922) demonstrated safety and resulted in a 50% (26/52) overall response rate in patients with ALK-positive or ROS1-positive non-small cell lung cancer, including intracranial responses in patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 9009)).	detail...
ALK fusion	lung non-small cell carcinoma	sensitive	Lorlatinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865).	detail... 30413378 detail...
ALK fusion	lung non-small cell carcinoma	sensitive	Lorlatinib	Phase III	Actionable	In a Phase III trial (CROWN), Lorbrena (lorlatinib) treatment (n=149) demonstrated superior efficacy compared to Xalkori (crizotinib) (n=147) at 5-year follow-up in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients, with improved median progression-free survival (PFS, not reached vs 9.1 months, HR 0.19), 5-year PFS rate (60% vs 8%), and median time to intracranial progression (not reached vs 16.4 months) (PMID: 38819031; NCT03052608).	38819031
ALK fusion	lung non-small cell carcinoma	sensitive	Lorlatinib	FDA approved - On Companion Diagnostic	Actionable	In a Phase III trial (Study B7461006) that supported FDA approval, first-line Lorbrena (lorlatinib) treatment resulted in a significantly improved 12-mo progression-free survival rate (78% vs 39%, HR 0.28, p<0.0010) and a response rate of 76% (113/149) vs 58% (85/147) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer, and led to an intracranial response rate of 71% (12/14) vs 23% (3/13) in patients with measurable CNS metastases (PMID: 33207094; NCT03052608).	33207094 detail... detail...
ALK fusion	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in reduction of the brain metastases in a patient with ALK-positive lung adenocarcinoma who had been previously treated with Alecensa (alectinib) and Xalkori (crizotinib) (PMID: 35373538).	35373538
ALK fusion	Erdheim-Chester disease	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org).	detail...
ALK fusion	lung non-small cell carcinoma	sensitive	Ensartinib	Phase II	Actionable	In a Phase II trial, Ensartinib (X-396) treatment resulted in an objective response in 57% (43/75; all partial responses), and stable disease (SD) in 33% (25/75) of patients with crizotinib-refractory non-small cell lung cancer harboring an ALK fusion, with a response rate of 59% and SD rate of 31% in the 70 patients with EML4-ALK, and a response rate of 40% and SD rate of 60% in the 5 patients with non-EML4 ALK fusions (PMID: 31628085; NCT03215693).	31628085
ALK fusion	Advanced Solid Tumor	sensitive	Entrectinib	Case Reports/Case Series	Actionable	In a Phase I/II trial (STARTRK-NG), Rozlytrek (entrectinib) treatment was safe and resulted in an overall response rate (ORR) of 57.7% (15/26, 7 complete responses) with median duration of response and progression-free survival not reached in pediatric patients with CNS or extracranial solid tumors harboring fusions in NTRK1, NTRK2, NTRK3, ROS1, or ALK, ORR was 33.3% (1/3) in patients harboring ALK fusions (PMID: 35395680; NCT02650401).	35395680
ALK fusion	Advanced Solid Tumor	predicted - sensitive	Repotrectinib	Phase I	Actionable	In a Phase I (TRIDENT-1) trial, Augtyro (repotrectinib) treatment resulted in stable disease in 25% (4/16) of patient with advanced solid tumor harboring ALK fusions who completed 2 cycles of treatment (J Clin Oncol 36, 2018 (suppl; abstr 2513); NCT03093116).	detail...
ALK fusion	lung non-small cell carcinoma	predicted - sensitive	NVL-655	Phase I	Actionable	In a Phase I trial (ALKOVE-1), NVL-655 treatment demonstrated activity in patients with ALK-positive non-small cell lung cancer (including patients with ALK fusion with or without secondary ALK mutations), resulting in a response rate of 38% (39/103), a median duration of response (DOR) of 9.2 months, DOR greater than 6 months in 79% of patients, and a response rate of 39% (15/38) at the RP2D dose of 150mg (Ann Oncol (2024) 35 (suppl_2): S802-S803; NCT05384626).	detail...
ALK fusion	lung non-small cell carcinoma	predicted - sensitive	APG-2449	Phase I	Actionable	In a Phase I trial, APG-2449 treatment was well tolerated and resulted in preliminary efficacy with 4 partial responses among 14 patients with non-small cell lung cancer harboring an ALK fusion who previously progressed on a second-generation ALK inhibitor, 1 intracranial complete response and 3 partial responses among 8 patients with brain metastases, and an overall response rate of 80% and a disease control rate of 100% among 10 TKI-naive patients (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 9071-9071).	detail...
ALK fusion	lung non-small cell carcinoma	sensitive	TQ-B3139	Phase I	Actionable	In a Phase I trial, TQ-B3139 (CT-711) treatment demonstrated safety and resulted in an overall response rate (ORR) of 61.9% (39/63), an intracranial ORR of 70% (7/10), disease control rate of 84.1% (53/63), and median progression-free survival (PFS) of 19.0 months in patients with non-small cell lung cancer harboring an ALK fusion or ROS1 fusion, with TKI-naive patients demonstrating a longer PFS (25.2 mo vs 5.4 mo, p=0.02) (PMID: 35940055; NCT03099330).	35940055
ALK fusion	anaplastic large cell lymphoma	predicted - sensitive	Crizotinib + Cyclophosphamide + Cytarabine + Dexamethasone + Doxorubicin + Etoposide + Ifosfamide + Methotrexate	Phase II	Actionable	In a Phase II trial (ANHL12P1), the addition of Xalkori (crizotinib) to standard chemotherapy prevented disease relapse in pediatric patients with ALK fusion-positive anaplastic large cell lymphoma, with an event-free survival rate of 76.8%, a 2-year overall survival of 95.2%, and a complete response rate among evaluable patients of 91.7% (55/60) after 2 cycles and 98.3% (59/60) after 6 cycles (PMID: 36534942; NCT01979536).	36534942
ALK fusion ALK D1203N ALK E1210K ALK G1269A	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1269A was identified as an acquired mutation in a non-small cell lung cancer patient harboring an ALK fusion with ALK D1203N and ALK E1210K who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063).	35726063
EML4 - ALK ALK A1200V	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK A1200V was identified at progression on Xalkori (crizotinib) in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 34058070).	34058070
ALK F1174C	neuroblastoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a partial response in a neuroblastoma patient harboring ALK F1174C, along with CDKN2A A102V (PMID: 37147298; NCT03107988).	37147298
ALK F1174C	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1174C in an in vitro assay (PMID: 34158340).	34158340
ALK F1174C	neuroblastoma	predicted - sensitive	Cyclophosphamide + Doxorubicin + Lorlatinib + Vincristine Sulfate	Preclinical - Pdx	Actionable	In a preclinical study, the combination of Lorbrena (lorlatinib), Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), and Oncovin (vincristine) resulted in modest inhibition of tumor growth in a patient-derived xenograft (PDX) model of neuroblastoma harboring ALK F1174C (PMID: 36602782).	36602782
EML4 - ALK ALK F1174C	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of a cell line expressing EML4-ALK with ALK F1174C in culture (PMID: 31446141).	31446141
EML4 - ALK ALK F1174C	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) modestly inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 35421578).	35421578
EML4 - ALK ALK F1174C	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response and a progression-free survival of 29 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) with ALK F1174C (PMID: 38978737).	38978737
EML4 - ALK ALK F1174C	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a retrospective analysis, Alecensa (alectinib) treatment resulted in a partial response with a progression-free survival of 13.4 months, overall survival of 25.9 months, and a duration of treatment of 14.5 months in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20) and ALK F1174C (PMID: 39500140).	39500140
EML4 - ALK ALK F1174C	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C demonstrated decreased sensitivity to Alecensa (alectinib) in culture compared to cells expressing EML4-ALK with wild-type ALK (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C demonstrated sensitivity to Alecensa (alectinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK F1174C	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) progressed on treatment with Xalkori (crizotinib) and was found to have acquired ALK F1174C (PMID: 38978737).	38978737
EML4 - ALK ALK F1174C	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C	lung non-small cell carcinoma	resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who developed resistance to Xalkori (crizotinib) treatment was subsequently treated with Zykadia (ceritinib), eventually progressed, and was found to have acquired ALK F1174C (PMID: 24675041).	24675041
EML4 - ALK ALK F1174C	Advanced Solid Tumor	conflicting	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C	Advanced Solid Tumor	conflicting	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were sensitive to treatment with Zykadia (ceritinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK F1174C	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in stable disease lasting 6 months in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20) and ALK F1174C, who previously progressed on Xalkori (crizotinib) and Alunbrig (brigatinib) (PMID: 36093526).	36093526
EML4 - ALK ALK F1174C	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 35421578).	35421578
EML4 - ALK ALK F1174C ALK L1198F	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C ALK L1198F	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C ALK L1198F	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C ALK L1198F	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C ALK L1198F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK F1174C ALK D1203N	Advanced Solid Tumor	decreased response	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK F1174C ALK D1203N	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK F1174C ALK D1203N	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK F1174C ALK D1203N	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK F1174C ALK D1203N	Advanced Solid Tumor	decreased response	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Lorlatinib (PF-06463922) in culture compared to cells expressing wild-type EML4-ALK (PMID: 27432227).	27432227
EML4 - ALK ALK F1174C ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK F1174C in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK F1174C ALK E1210K	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring EML4-ALK, ALK F1174C, and ALK E1210K (PMID: 34378333).	34378333
ALK F1174C TP53 wild-type	neuroblastoma	resistant	Idasanutlin + Lorlatinib	Preclinical - Pdx	Actionable	In a preclinical study, a patient-derived xenograft (PDX) model of TP53 wild-type neuroblastoma harboring ALK F1174C was resistant to combination treatment with Lorbrena (lorlatinib) and Idasanutlin (RG7388) (PMID: 36602782).	36602782
EML4 - ALK ALK F1174C ALK V1180L	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) and ALK F1174C progressed on treatment with Alecensa (alectinib) and was found to have acquired ALK V1180L (PMID: 38978737).	38978737
EML4 - ALK ALK F1174C ALK V1180L	lung adenocarcinoma	predicted - sensitive	Bevacizumab + Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, treatment with the combination of Lorbrena (lorlatinib) and Avastin (bevacizumab) resulted in a partial response and a progression-free survival of 33 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) with ALK F1174C and V1180L (PMID: 38978737).	38978737
ALK F1174I	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK F1174I in culture (PMID: 27483357).	27483357
EML4 - ALK ALK F1174I	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1174I	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1174I	Advanced Solid Tumor	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174I demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1174I	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1174I	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1174I	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174I were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1174I	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640).	33627640
ALK F1174V	neuroblastoma	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, neuroblastoma cells harboring ALK F1174V were sensitive to Alunbrig (brigatinib) in culture and in vivo, resulting in inhibition of both Alk activity and cell proliferation (PMID: 27049722).	27049722
ALK F1174V	neuroblastoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, a patient harboring ALK F1174V stayed on treatment for 3 cycles until disease progression (PMID: 33568345; NCT00939770).	33568345
ALK F1174V	neuroblastoma	sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response lasting greater than 20 months in a patient with neuroblastoma harboring ALK F1174V (PMID: 37561984).	37561984
ALK F1174V	neuroblastoma	sensitive	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment inhibited proliferation of a neuroblastoma cell line harboring ALK F1174V in culture and inhibited tumor growth in a cell line xenograft model (PMID: 27483357).	27483357
ALK F1174V	neuroblastoma	sensitive	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Rozlytrek (entrectinib) treatment inhibited ALK phosphorylation, downstream signaling, and viability of a neuroblastoma cell line harboring ALK F1174V in culture (PMID: 35085006).	35085006
ALK F1174V	neuroblastoma	predicted - resistant	Repotrectinib	Preclinical - Pdx	Actionable	In a preclinical study, a neuroblastoma patient-derived xenograft (PDX) model harboring ALK F1174V was resistant to treatment with Augtyro (repotrectinib) (PMID: 34482287).	34482287
ALK F1174V	neuroblastoma	predicted - sensitive	Irinotecan + Repotrectinib + Temozolomide	Preclinical - Pdx	Actionable	In a preclinical study, combination treatment with Augtyro (repotrectinib), Camptosar (irinotecan), and Temodar (temozolomide) resulted in inhibition of tumor growth in a patient-derived xenograft (PDX) model of neuroblastoma harboring ALK F1174V (PMID: 34482287).	34482287
EML4 - ALK ALK F1174V	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK F1174V in the context of EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK F1174V	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1174V	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 35421578).	35421578
EML4 - ALK ALK F1174V	lung non-small cell carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK initially responded to Xalkori (crizotinib), but then progressed due to acquisition of the secondary resistance mutation, ALK F1174V, and then responded to treatment with Alecensa (alectinib), demonstrating a complete response in one lung nodule and a 44% decrease in size in a second lung nodule (PMID: 26464158).	26464158
EML4 - ALK ALK F1174V	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1174V	lung non-small cell carcinoma	resistant	Crizotinib	Clinical Study	Actionable	In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response to Xalkori (crizotinib) treatment after 3 months, but then progressed, and was found to harbor the secondary resistance mutation, ALK F1174V (PMID: 24736079).	24736079
EML4 - ALK ALK F1174V	Advanced Solid Tumor	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK F1174V in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK F1174V	Advanced Solid Tumor	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174V demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1174V	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1174V	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a complete response with a progression-free survival of 12.3 months, overall survival of 28.1 months, and a duration of treatment of 13.8 months in a patient with lung adenocarcinoma harboring EML4-ALK (e2:e20) with ALK F1174V (PMID: 39500140).	39500140
EML4 - ALK ALK F1174V	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK F1174V in culture (PMID: 31446141).	31446141
EML4 - ALK ALK F1174V	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1174V	Advanced Solid Tumor	sensitive	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK F1174V in culture (PMID: 31446141).	31446141
EML4 - ALK ALK F1174V	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174V were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1174V	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1174V	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 35421578).	35421578
EML4 - ALK ALK I1171S ALK F1174V	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK F1174V initially responded to Alecensa (alectinib), but then demonstrated progression in one of two lung nodules, which was found to harbor a secondary resistance mutation, ALK I1171S, and upon resection of the nodule the patient continued Alecensa (alectinib) treatment and achieved complete remission (PMID: 26464158).	26464158
EML4 - ALK ALK I1171T ALK F1174V	lung non-small cell carcinoma	predicted - sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment resulted in a partial response in a patient with non-small cell lung cancer harboring EML4-ALK (e13:e20), ALK F1174V, and ALK I1171T (PMID: 34890832; NCT01283516).	34890832
EML4 - ALK	lung adenocarcinoma	sensitive	Alvocidib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alvocidib (flavopiridol) treatment induced cell cycle arrest and apoptosis, reduced viability, and inhibited proliferation in both a parental lung adenocarcinoma cell line and isogenic lung adenocarcinoma cell lines resistant to Xalkori (crizotinib), Zykadia (ceritinib), and Alecensa (alectinib), all harboring EML4-ALK, in culture, and reduced tumor growth in Xalkori (crizotinib) and Alecensa (alectinib)-resistant cell line xenograft models (PMID: 32558295).	32558295
EML4 - ALK	lung squamous cell carcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in a complete response in the lung and partial response in the brain lesions in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK, with a progression-free survival of 11 months (PMID: 34376997).	34376997
EML4 - ALK	lung non-small cell carcinoma	sensitive	Brigatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited Alk phosphorylation and growth in non-small cell lung cancer cell lines harboring EML4-ALK in culture, and induced near complete tumor regression in cell line xenograft models (PMID: 27780853).	27780853
EML4 - ALK	lung non-small cell carcinoma	sensitive	Brigatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited tumor growth in a non-small cell lung cancer cell line xenograft model harboring EML4-ALK (PMID: 37036582).	37036582
EML4 - ALK	lung adenocarcinoma	sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in a complete response with a reduction in the brain metastases in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 38158887).	38158887
EML4 - ALK	lung adenocarcinoma	sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in a progression-free survival of 3.2 months in a patient with lung adenocarcinoma harboring EML4-ALK (e20:e20) and inhibited growth of a patient-derived organoid cell line in culture (PMID: 38983150).	38983150
EML4 - ALK	lung adenocarcinoma	sensitive	Brigatinib	Preclinical - Pdx	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment decreased tumor growth in a patient-derived xenograft (PDX) model of lung adenocarcinoma harboring EML4-ALK (PMID: 34911818).	34911818
EML4 - ALK	large cell neuroendocrine carcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in a response in the primary tumor and brain metastases in a patient with large cell neuroendocrine carcinoma of the lung harboring EML4-ALK (e6:e20) (PMID: 39395329).	39395329
EML4 - ALK	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing EML4-ALK in culture (PMID: 25228534).	25228534
EML4 - ALK	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 35421578).	35421578
EML4 - ALK	mucosal melanoma	sensitive	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, ASP3026 decreased viability of a mucosal melanoma cell line harboring EML4-ALK in culture (PMID: 29054983).	29054983
EML4 - ALK	Advanced Solid Tumor	sensitive	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, ASP3026 inhibited growth of a transformed cell line expressing EML4-ALK in culture (PMID: 25228534).	25228534
EML4 - ALK	colon adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in clinical improvement after 1 month and a partial response lasting 8 months in a patient with colon adenocarcinoma harboring EML4-ALK (PMID: 33776709).	33776709
EML4 - ALK	colon adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in shrinkage of the pulmonary and mediastinal lymph node metastases in a patient with colon adenocarcinoma harboring EML4-ALK (PMID: 38381603).	38381603
EML4 - ALK	sarcoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a Phase II trial, Alecensa (alectinib) treatment resulted in a partial response in a patient with metastatic non-myofibroblastic sarcoma harboring EML4-ALK (e2:e20) (PMID: 39188081).	39188081
EML4 - ALK	lung cancer	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response in a patient with metastatic lung cancer harboring EML4-ALK (PMID: 34378333).	34378333
EML4 - ALK	pancreatic cancer	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in stable primary disease and decrease in brain lesions with treatment lasting nearly 10 months before progression of the brain metastases in a patient with pancreatic cancer harboring EML4-ALK (PMID: 34568053).	34568053
EML4 - ALK	osteosarcoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in stable disease lasting at least 400 days in a patient with metastatic osteosarcoma harboring EML4-ALK (PMID: 38096470).	38096470
EML4 - ALK	lung squamous cell carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response lasting 9.5 months in a patient with metastatic squamous cell lung cancer harboring EML4-ALK (PMID: 34324792).	34324792
EML4 - ALK	lung non-small cell carcinoma	sensitive	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited Alk phosphorylation and growth of a human non-small cell lung cancer cell line harboring EML4-ALK in culture and in cell line xenograft models (PMID: 21575866).	21575866
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response lasting 17.5 months in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 34911818).	34911818
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response lasting 6.5 months in a patient with lung adenocarcinoma harboring EML4-ALK, who also harbored IDH1 R132H (PMID: 35324529).	35324529
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response within three months, with a reduction in liver metastases, in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e20) (PMID: 36864442).	36864442
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a radiological response after 8 weeks with a 50% decrease in tumor size in a pregnant patient with metastatic lung adenocarcinoma harboring EML4-ALK, and normal fetal development was observed (PMID: 38057186).	38057186
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a response lasting 24 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e19) who previously progressed on Xalkori (crizotinib) (PMID: 29981924).	29981924
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in clinical symptom improvement and a partial response lasting at least 9 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e18) (PMID: 34763318).	34763318
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, neoadjuvant Alecensa (alectinib) treatment resulted in a complete pathological response in one patient with lung adenocarcinoma harboring EML4-ALK after 6 weeks and a major pathological response in another patient after 12 weeks of treatment, allowing for surgical resection in both (PMID: 36075183).	36075183
EML4 - ALK	renal cell carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a significant response in the brain and lung metastases in a patient with renal cell carcinoma harboring EML4-ALK (PMID: 29079636).	29079636
EML4 - ALK	papillary renal cell carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical study, three previously treated patients with metastatic papillary renal cell carcinoma harboring an EML4-ALK fusion were sensitive to treatment with Alecensa (alectinib), demonstrating a clinical and radiographic response in one patient, a radiographic response and ongoing stable disease for 9 months in another patient, and regression of multiple metastatic sites in the third patient (PMID: 29685646).	29685646
EML4 - ALK	pulmonary neuroendocrine tumor	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with metastatic neuroendocrine carcinoma of the lung harboring EML4-ALK demonstrated a favorable response to Alecensa (alectinib), despite the appearance of new brain and adrenal lesions that were resolved with radiotherapy, and remained on treatment for at least 60 months (PMID: 36690569).	36690569
EML4 - ALK	pulmonary neuroendocrine tumor	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in significant response in the lung and brain lesions in 2 patients with metastatic pulmonary atypical carcinoid tumor harboring EML4-ALK (e6:e20 or e13:e20), with progression-free survival of 6 and 9 months (PMID: 35832448).	35832448
EML4 - ALK	malignant pleural mesothelioma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in symptom improvement and a partial response lasting 3.5 months in a patient with malignant pleural mesothelioma harboring EML4-ALK (PMID: 32600123).	32600123
EML4 - ALK	salivary gland cancer	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in an ongoing complete response after 8 months of treatment, with complete resolution of metastatic liver lesions, in a patient with metastatic salivary ductal carcinoma harboring EML4-ALK (PMID: 37041305).	37041305
EML4 - ALK	duodenum adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response with 57% tumor reduction after 49 days in a patient with metastatic duodenum adenocarcinoma harboring EML4-ALK, who remained on treatment and progression-free at 6 months (PMID: 36713517).	36713517
EML4 - ALK	large cell neuroendocrine carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response after 1 month of treatment in a patient with lung large cell neuroendocrine carcinoma harboring EML4-ALK (e13:e20), with response lasting at least 12 months (PMID: 36819595).	36819595
EML4 - ALK	large cell neuroendocrine carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response after 2 months of treatment in a patient with metastatic large cell neuroendocrine carcinoma harboring EML4-ALK (e20:e20), with response ongoing at 32 months (PMID: 38023218).	38023218
EML4 - ALK	large cell neuroendocrine carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in clinical improvement with a partial response including dramatic shrinkage in all of the known lesions in a patient with large cell lung neuroendocrine cancer and brain metastasis harboring EML4-ALK (PMID: 35280726).	35280726
EML4 - ALK	large cell neuroendocrine carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in significant clinical improvement and a partial response in a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK after 4 weeks of therapy, however, progression in bone metastasis developed at 4 months (PMID: 34994612).	34994612
EML4 - ALK	large cell neuroendocrine carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, second-line Alecensa (alectinib) treatment resulted in a partial response lasting 10 months in a patient with metastatic large cell neuroendocrine lung carcinoma harboring EML4-ALK (e20:e20) (PMID: 36207130).	36207130
EML4 - ALK	inflammatory myofibroblastic tumor	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a decrease or disappearance of metastatic lesions after 10 months in a patient with inflammatory myofibroblastic tumor harboring EML4-ALK (e6:e20), who remained on treatment with good clinical condition at 16 months (PMID: 35280868).	35280868
EML4 - ALK	inflammatory myofibroblastic tumor	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a near-complete radiographic response after 3 months in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK (PMID: 37255276).	37255276
EML4 - ALK	inflammatory myofibroblastic tumor	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in shrinkage of the primary tumor and brain metastasis in a patient with inflammatory myofibroblastic tumor harboring EML4-ALK (PMID: 38213097).	38213097
EML4 - ALK	mucosal melanoma	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) decreased viability of a mucosal melanoma cell line harboring EML4-ALK in culture (PMID: 29054983).	29054983
EML4 - ALK	lung mucoepidermoid carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment beginning at 33 weeks gestation in a pregnant patient with metastatic mucoepidermoid carcinoma harboring EML4-ALK resulted in a near complete response during the postpartum period, and did not result in fetal or developmental anomalies for at least the first 11 months post birth (PMID: 34543940).	34543940
EML4 - ALK	ovarian serous carcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in decreased CA-125 and complete remission lasting more than 1 year in a patient with metastatic high-grade serous ovarian cancer harboring EML4-ALK (E13:E20), who previously progressed on chemotherapy (PMID: 32845005).	32845005
EML4 - ALK	Smarca4-deficient sarcoma of thorax	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response after 6 weeks and a complete remission after 9 months of therapy in a patient with SMARCA4-deficient undifferentiated tumor of the thorax harboring EML4-ALK (e13:e20) (PMID: 36969551).	36969551
EML4 - ALK	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 26698910).	26698910
EML4 - ALK	neuroendocrine tumor	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, first-line treatment with Xalkori (crizotinib) resulted in shrinkage of the lung and adrenal gland lesions in a patient with a neuroendocrine tumor, consistent with atypical carcinoid tumor, harboring EML4-ALK (PMID: 30154667).	30154667
EML4 - ALK	neuroblastoma	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing EML4-ALK in culture (PMID: 26554404).	26554404
EML4 - ALK	pancreatic cancer	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in tumor shrinkage with treatment lasting eight months in a patient with pancreatic cancer harboring EML4-ALK (PMID: 34568053).	34568053
EML4 - ALK	lung squamous cell carcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment with whole-brain radiotherapy resulted in a partial response with a progression-free survival of 17 months in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK (PMID: 34376997).	34376997
EML4 - ALK	lung non-small cell carcinoma	sensitive	Crizotinib	Clinical Study - Cohort	Actionable	In a clinical study, non-small cell lung carcinoma patients harboring an EML4-ALK variant 1 (E13; A20, n=19) demonstrated a significantly longer progression-free survival (11.0 vs 4.2 months, p<0.05) compared to patients with a non-variant 1 EML4-ALK fusion (n=16) when treated with Xalkori (crizotinib) (PMID: 27354483).	27354483
EML4 - ALK	lung non-small cell carcinoma	sensitive	Crizotinib	Phase I	Actionable	In a Phase I trial, Xalkori (crizotinib) inhibited tumor growth by at least 30% from baseline in 90% (18/20) of patients with EML4-ALK positive non-small cell lung carcinoma (PMID: 20979469; NCT00585195).	20979469
EML4 - ALK	lung non-small cell carcinoma	sensitive	Crizotinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited tumor growth in a non-small cell lung cancer cell line xenograft model harboring EML4-ALK (PMID: 37036582).	37036582
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK variant 8 achieved a pathologic complete response following treatment with Xalkori (crizotinib), with a reduction in primary tumor size and pleural metastases within 1 month of treatment, and continuation of treatment for 5 years until death, after which cancer was not observed at autopsy (PMID: 31690489).	31690489
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in a complete response and a progression-free survival of 35 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) (PMID: 38978737).	38978737
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20) (PMID: 36093526).	36093526
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (PMID: 36324562).	36324562
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in a response lasting 19 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e19) (PMID: 29981924).	29981924
EML4 - ALK	medullary thyroid carcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in a decrease in the lung, liver, and bone lesions in a patient with metastatic medullary thyroid carcinoma harboring EML4-ALK (e13:e20) that was treated on a Phase I clinical trial (PMID: 26295973; NCT01121588).	26295973
EML4 - ALK	clear cell renal cell carcinoma	sensitive	Crizotinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Xalkori (crizotinib) treatment inhibited tumor growth in a cell line xenograft model of clear cell renal cell carcinoma expressing EML4-ALK (PMID: 32020234).	32020234
EML4 - ALK	large cell neuroendocrine carcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in regression of all previously identified lesions in a patient with large cell neuroendocrine carcinoma harboring EML4-ALK (PMID: 30154667).	30154667
EML4 - ALK	large cell neuroendocrine carcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in stable disease with early progression after 3 months in a patient with metastatic large cell neuroendocrine lung carcinoma harboring EML4-ALK (e20:e20) (PMID: 36207130).	36207130
EML4 - ALK	inflammatory myofibroblastic tumor	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with inflammatory myofibroblastic tumor harboring EML4-ALK achieved complete remission three years after starting Xalkori (crizotinib) treatment (PMID: 26808369).	26808369
EML4 - ALK	inflammatory myofibroblastic tumor	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in tumor shrinkage with response lasting at least 28 months in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK (PMID: 36035049).	36035049
EML4 - ALK	mucosal melanoma	sensitive	Crizotinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited downstream signaling and decreased viability of a mucosal melanoma cell line expressing EML4-ALK in culture and inhibited tumor growth in a cell line xenograft model (PMID: 29054983).	29054983
EML4 - ALK	colorectal carcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in rapid clinical benefit and a partial response after 1 month of therapy in a patient with metastatic colorectal carcinoma harboring EML4-ALK, until disease progression after 4 months (PMID: 34036227).	34036227
EML4 - ALK	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 30002191).	30002191
EML4 - ALK	lung adenocarcinoma	sensitive	Dinaciclib	Preclinical - Cell culture	Actionable	In a preclinical study, Dinaciclib (SCH 727965) treatment induced apoptosis, reduced viability, and inhibited proliferation in parental lung adenocarcinoma cells, and isogenic cells resistant to Xalkori (crizotinib), Zykadia (ceritinib), and Alecensa (alectinib), all harboring EML4-ALK in culture (PMID: 32558295).	32558295
EML4 - ALK	breast cancer	resistant	Fulvestrant	Preclinical - Cell culture	Actionable	In a preclinical study, breast cancer cells expressing EML4-ALK demonstrated resistance to treatment with Faslodex (fulvestrant) in culture (PMID: 32348852).	32348852
EML4 - ALK	breast cancer	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, breast cancer cells expressing EML4-ALK were sensitive to treatment with Zykadia (ceritinib) in culture, demonstrating inhibition of cell growth (PMID: 32348852).	32348852
EML4 - ALK	lung non-small cell carcinoma	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited phosphorylation of Alk and inhibited growth of human non-small cell lung cancer cell lines harboring EML4-ALK in culture (PMID: 25173427).	25173427
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, Zykadia (ceritinib) treatment in a pediatric patient with metastatic lung adenocarcinoma harboring EML4-ALK resulted in a very good partial response at 2 months with regression of enlarged lymph nodes, with a near-complete response after 18 months of treatment (PMID: 36640634).	36640634
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, Zykadia (ceritinib) treatment resulted in a partial response lasting 8.7 months in a patient with lung adenocarcinoma harboring EML4-ALK, who progressed on prior Alecensa (alectinib) treatment (PMID: 34911818).	34911818
EML4 - ALK	mucosal melanoma	sensitive	Ceritinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Zykadia (ceritinib) decreased viability of a mucosal melanoma cell line harboring EML4-ALK in culture and inhibited tumor growth in a cell line xenograft model (PMID: 29054983).	29054983
EML4 - ALK	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK in culture (PMID: 25228534).	25228534
EML4 - ALK	neuroblastoma	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells harboring EML4-ALK in culture (PMID: 26554404).	26554404
EML4 - ALK	osteosarcoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in stable disease for nearly 60 weeks in a patient with metastatic osteosarcoma harboring EML4-ALK, who previously progressed on Alecensa (alectinib) treatment (PMID: 38096470).	38096470
EML4 - ALK	lung non-small cell carcinoma	sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase III trial (CROWN), Lorbrena (lorlatinib) therapy resulted in an objective response rate (ORR) of 81% (120/149, 15 complete and 105 partial responses) and a median progression-free survival (mPFS) that was not reached at 5-year follow-up in ALK-positive non-small cell lung cancer patients, with an ORR of 80%, 100%, and 83% and an mPFS of 64.3 mo, not reached, and 60.0 mo in patients with EML4-ALK variants 1 (n=20), 2 (n=7), and 3a/b (n=18), respectively (PMID: 38819031; NCT03052608).	38819031
EML4 - ALK	lung non-small cell carcinoma	sensitive	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and proliferation of non-small cell lung carcinoma cells harboring EML4-ALK fusion, and reduced intracranial tumor size in cell line xenograft models (PMID: 26144315).	26144315
EML4 - ALK	lung adenocarcinoma	sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a progression-free survival of 1.9 months in a patient with lung adenocarcinoma harboring EML4-ALK (e20:e20) and inhibited growth of a patient-derived organoid cell line in culture (PMID: 38983150).	38983150
EML4 - ALK	lung adenocarcinoma	sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in an intracranial response, with improvement of the metastatic brain lesions, in a patient with lung adenocarcinoma harboring EML4-ALK (e20:e20), who previously progressed on Alunbrig (brigatinib) (PMID: 38924375).	38924375
EML4 - ALK	lung adenocarcinoma	sensitive	Lorlatinib	Preclinical - Pdx	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment decreased tumor growth in a patient-derived xenograft (PDX) model of lung adenocarcinoma harboring EML4-ALK (PMID: 34911818).	34911818
EML4 - ALK	lung mucoepidermoid carcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with metastatic pulmonary mucoepidermoid carcinoma harboring EML4-ALK (e6:e20) (PMID: 39259069).	39259069
EML4 - ALK	lung mucoepidermoid carcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with pulmonary mucoepidermoid carcinoma harboring EML4-ALK (e20:e20) (PMID: 39267825).	39267825
EML4 - ALK	colorectal carcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in clinical benefit and a progression-free survival of 11.5 months in a patient with metastatic colorectal carcinoma harboring EML4-ALK, whose disease progressed on initial Xalkori (crizotinib) treatment and did not respond to subsequent Alecensa (alectinib) treatment (PMID: 34036227).	34036227
EML4 - ALK	epithelioid inflammatory myofibroblastic sarcoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a pathological complete response in a patient with epithelioid inflammatory myofibroblastic sarcoma harboring EML4-ALK (e6:e20) (PMID: 39144623).	39144623
EML4 - ALK	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 26698910).	26698910
EML4 - ALK	lung non-small cell carcinoma	sensitive	Ensartinib	Phase II	Actionable	In a Phase II trial, Ensartinib (X-396) treatment resulted in an objective response in 59% (41/70; all partial responses) and stable disease in 31% (22/70) of patients with crizotinib-refractory non-small cell lung cancer harboring EML4-ALK (PMID: 31628085; NCT03215693).	31628085
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a clinical case study, neoadjuvant Ensartinib (X-396) resulted in a major pathological response and decreased tumor size allowing for resection 5 months after treatment intitation in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 36730477).	36730477
EML4 - ALK	intrahepatic cholangiocarcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a clinical case study, Ensartinib (X-396) treatment resulted in a partial response with tumor regression in a patient with metastatic intrahepatic cholangiocarcinoma harboring EML4-ALK (PMID: 37675235).	37675235
EML4 - ALK	Advanced Solid Tumor	sensitive	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ensartinib (X-396) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 30002191).	30002191
EML4 - ALK	lung non-small cell carcinoma	sensitive	Entrectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, non-small cell lung carcinoma cells harboring EML4-ALK were sensitive to Rozlytrek (entrectinib), resulting in inhibition of cell proliferation and complete tumor regression in cell line xenograft models (PMID: 26939704).	26939704
EML4 - ALK	mucosal melanoma	sensitive	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Rozlytrek (entrectinib) decreased viability of a mucosal melanoma cell line harboring EML4-ALK in culture (PMID: 29054983).	29054983
EML4 - ALK	Advanced Solid Tumor	sensitive	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 33627640).	33627640
EML4 - ALK	lung non-small cell carcinoma	sensitive	TAE226	Preclinical	Actionable	In a preclinical study, TAE226 treatment inhibited proliferation of non-small cell lung carcinoma cell lines harboring EML4-ALK fusion in culture (PMID: 26090892).	26090892
EML4 - ALK	lung non-small cell carcinoma	sensitive	CEP-28122	Preclinical - Cell line xenograft	Actionable	In a preclinical study, CEP-28122 inhibited growth of non-small cell lung carcinoma cell lines harboring EML4-ALK in culture, and resulted in tumor regression in cell line xenograft models (PMID: 22203728).	22203728
EML4 - ALK	lung cancer	sensitive	X-376	Preclinical - Cell line xenograft	Actionable	In a preclinical study, X-376 inhibited Alk signaling, resulted in growth inhibition in lung cancer cells harboring EML4-ALK fusion in culture and in cell line xenograft models (PMID: 21613408).	21613408
EML4 - ALK	lung non-small cell carcinoma	sensitive	Ensartinib + Sirolimus	Preclinical	Actionable	In a preclinical study, transformed non-small cell lung cancer cells harboring EML4-ALK demonstrated enhanced growth inhibition to a combination treatment with Afinitor (sirolimus) and Ensartinib (X-396) (PMID: 21613408).	21613408
EML4 - ALK	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 33627640).	33627640
EML4 - ALK	lung non-small cell carcinoma	sensitive	Afatinib + Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of Gilotrif (afatinib) and Xalkori (crizotinib) increased inhibition of downstream signaling, viability, and residual colony formation in a non-small cell lung cancer cell line harboring EML4-ALK compared to Xalkori (crizotinib) treatment alone in culture (PMID: 37748191).	37748191
EML4 - ALK	lung adenocarcinoma	sensitive	THZ1	Preclinical - Cell culture	Actionable	In a preclinical study, THZ1 treatment reduced viability and inhibited proliferation of parental lung adenocarcinoma, and isogenic cells resistant to Xalkori (crizotinib), Zykadia (ceritinib), and Alecensa (alectinib) cells, all harboring EML4-ALK, in culture (PMID: 32558295).	32558295
EML4 - ALK	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Augtyro (repotrectinib) inhibited growth of transformed cells expressing EML4-ALK in culture, led to tumor growth inhibition in cell line xenograft models (PMID: 30093503).	30093503
EML4 - ALK	Advanced Solid Tumor	sensitive	Taletrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK were sensitive to treatment with Taletrectinib (DS6051b) in culture, demonstrating cell growth inhibition (PMID: 31399568).	31399568
EML4 - ALK	lung non-small cell carcinoma	sensitive	Afatinib + Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, combination of Gilotrif (afatinib) and Alecensa (alectinib) restored sensitivity to Alecensa (alectinib) in non-small cell lung cancer cells harboring EML4-ALK fusion that acquired resistance to Alecensa (alectinib) through up-regulating Egfr signaling in culture and inhibited tumor progression in cell line xenograft models (PMID: 26682573).	26682573
EML4 - ALK	lung non-small cell carcinoma	sensitive	Afatinib + Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with the combination of Gilotrif (afatinib) and Alecensa (alectinib) increased inhibition of downstream signaling, viability, and residual colony formation in a non-small cell lung cancer cell line harboring EML4-ALK compared to Alecensa (alectinib) treatment alone in culture (PMID: 37748191).	37748191
EML4 - ALK	lung non-small cell carcinoma	predicted - sensitive	Crizotinib + Filgotinib	Preclinical - Cell culture	Actionable	In a preclinical study, non-small cell lung carcinoma cells harboring EML4-ALK in culture that had, over time, acquired resistance to Xalkori (crizotinib) showed decreased drug resistance when treatment was combined with Filgotinib (GLPG0634), demonstrating reduced expression of Osmr and phosphorylated-Stat3, and decreased cell viability (PMID: 28729401).	28729401
EML4 - ALK	lung non-small cell carcinoma	sensitive	Iruplinalkib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Iruplinalkib (WX-0593) inhibited tumor growth in a non-small cell lung cancer cell line xenograft model harboring EML4-ALK (PMID: 37036582).	37036582
EML4 - ALK	lung non-small cell carcinoma	sensitive	Iruplinalkib	Preclinical - Pdx	Actionable	In a preclinical study, Iruplinalkib (WX-0593) inhibited tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK (PMID: 35421578).	35421578
EML4 - ALK	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 35421578).	35421578
EML4 - ALK	lung non-small cell carcinoma	sensitive	MTI-31	Preclinical - Cell line xenograft	Actionable	In a preclinical study, MTI-31 inhibited proliferation and migration and increased PD-L1 degradation in a non-small cell lung cancer cell line harboring EML4-ALK in culture, and inhibited tumor growth in xenograft models (PMID: 30796032).	30796032
EML4 - ALK	breast cancer	predicted - sensitive	Ceritinib + Fulvestrant	Preclinical - Cell culture	Actionable	In a preclinical study, the addition of Zykadia (ceritinib) to Faslodex (fulvestrant) treatment in breast cancer cells expressing EML4-ALK restored growth inhibition in culture (PMID: 32348852).	32348852
EML4 - ALK	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Alvocidib + Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alvocidib (flavopiridol) treatment in combination with Xalkori (crizotinib) reduced viability of Xalkori (crizotinib)-resistant lung adenocarcinoma cells harboring EML4-ALK in culture, but did not result in synergistic effects (PMID: 32558295).	32558295
EML4 - ALK	lung cancer	predicted - sensitive	Bevacizumab + Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, a lung cancer patient with brain metastases harboring EML4-ALK who had developed resistance to treatment with Lorbrena (lorlatinib) after three months was subsequently treated with a combination of Avastin (bevacizumab) and Lorbrena (lorlatinib), and demonstrated a best response of stable disease, including disease control for 5.4 months, and 8% tumor shrinkage in the brain (PMID: 33283131).	33283131
EML4 - ALK	lung non-small cell carcinoma	sensitive	Lorlatinib + PF-07284892	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of PF-07284892 and Lorbrena (lorlatinib) inhibited Erk phosphorylation in non-small cell lung cancer cells harboring EML4-ALK that was resistant to Lorbrena (lorlatinib), and induced tumor regression in a cell line xenograft model (PMID: 37269335).	37269335
EML4 - ALK	lung non-small cell carcinoma	sensitive	Alectinib + SHP099	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of Alecensa (alectinib) and SHP099 inhibited downstream signaling and synergistically inhibited proliferation in non-small cell lung cancer cell lines harboring EML4-ALK in culture, and resulted in increased suppression of tumor growth in cell line xenograft models compared to either agent alone (PMID: 34158345).	34158345
EML4 - ALK	lung non-small cell carcinoma	sensitive	Alectinib + Selumetinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of Alecensa (alectinib) and Koselugo (selumetinib) inhibited tumor growth in cell line xenograft models of non-small cell lung cancer harboring EML4-ALK, but was less potent compared to treatment with the combination of Alecensa (alectinib) and SHP099 (PMID: 34158345).	34158345
EML4 - ALK	lung non-small cell carcinoma	sensitive	Alectinib + RMC-4550	Preclinical - Cell culture	Actionable	In a preclinical study, the combination of Alecensa (alectinib) and RMC-4550 inhibited cell growth and downstream signaling in non-small cell lung cancer cell lines harboring EML4-ALK in culture (PMID: 34158345).	34158345
EML4 - ALK	lung non-small cell carcinoma	sensitive	NVL-655	Preclinical - Cell line xenograft	Actionable	In a preclinical study, NVL-655 inhibited growth of a patient-derived non-small cell lung cancer cell line harboring EML4-ALK in culture and inhibited growth of a cell line xenograft model (PMID: 39269178).	39269178
EML4 - ALK	lung adenocarcinoma	sensitive	NVL-655	Case Reports/Case Series	Actionable	In a Phase I trial (ALKOVE-1), NVL-655 treatment resulted in a complete response in the central nervous system metastases and an overall partial response with treatment ongoing for at least 9 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (PMID: 39269178; NCT05384626).	39269178
EML4 - ALK	Advanced Solid Tumor	predicted - sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK in culture (PMID: 39269178).	39269178
EML4 - ALK	lung non-small cell carcinoma	sensitive	XMU-MP-5	Preclinical - Cell line xenograft	Actionable	In a preclinical study, XMU-MP-5 treatment decreased downstream signaling, induced apoptosis, and inhibited proliferation of non-small cell lung caner cells harboring EML4-ALK in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34845836).	34845836
EML4 - ALK	Advanced Solid Tumor	sensitive	XMU-MP-5	Preclinical - Cell culture	Actionable	In a preclinical study, XMU-MP-5 treatment decreased downstream signaling, induced apoptosis, and inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 34845836).	34845836
EML4 - ALK	lung non-small cell carcinoma	sensitive	APG-2449	Preclinical - Cell line xenograft	Actionable	In a preclinical study, APG-2449 inhibited proliferation of non-small cell lung cancer cell lines harboring EML4-ALK in culture and resulted in dose-dependent antitumor activity in a cell line xenograft model (PMID: 35820889).	35820889
EML4 - ALK	Advanced Solid Tumor	sensitive	APG-2449	Preclinical - Cell culture	Actionable	In a preclinical study, APG-2449 inhibited proliferation of cells expressing EML4-ALK in culture (PMID: 35820889).	35820889
EML4 - ALK	lung non-small cell carcinoma	sensitive	TQ-B3139	Preclinical - Cell line xenograft	Actionable	In a preclinical study, TQ-B3139 (CT-711) inhibited Alk signaling and proliferation and induced cell cycle arrest and apoptosis in non-small cell lung cancer cell lines harboring EML4-ALK in culture and induced tumor regression in cell line xenograft models (PMID: 30210922).	30210922
EML4 - ALK	Advanced Solid Tumor	sensitive	TQ-B3139	Preclinical - Cell line xenograft	Actionable	In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of cells expressing EML4-ALK in culture and inhibited tumor growth in a cell line xenograft model (PMID: 30210922).	30210922
EML4 - ALK	large cell neuroendocrine carcinoma	predicted - sensitive	Alectinib + Zoledronic acid	Case Reports/Case Series	Actionable	In a clinical case study, treatment with the combination of Alecensa (alectinib) and Zoledronic acid resulted in a partial response with progression-free survival ongoing at 21 months in a patient with metastatic large cell neuroendocrine carcinoma harboring EML4-ALK (e6:e20) (PMID: 38023218).	38023218
EML4 - ALK ALK G1269A	lung adenocarcinoma	sensitive	Brigatinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of patient-derived organoids of lung adenocarcinoma harboring EML4-ALK and ALK G1269A in culture and resulted in tumor shrinkage in a patient-derived xenograft (PDX) model (PMID: 38360931).	38360931
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 35421578).	35421578
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In preclinical studies, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859, PMID: 26698910).	26698910 27009859
EML4 - ALK ALK G1269A	Advanced Solid Tumor	resistant	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated moderate resistance to ASP3026 in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1269A	Advanced Solid Tumor	resistant	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK G1269A	lung non-small cell carcinoma	sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with EML4-ALK fusion positive non-small cell lung cancer with ALK G1269A had a partial response to Alecensa (alectinib) treatment (PMID: 26849637).	26849637
EML4 - ALK ALK G1269A	lung non-small cell carcinoma	sensitive	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited proliferation of a Xalkori (crizotinib)-resistant human non-small cell lung cancer cell line harboring an EML-ALK fusion with ALK G1269A in culture and induced tumor regression in cell line xenograft models (PMID: 26849637, PMID: 23344087).	26849637 23344087
EML4 - ALK ALK G1269A	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture, and inhibited tumor growth in xenograft models (PMID: 24887559).	24887559
EML4 - ALK ALK G1269A	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) modestly inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1269A	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to Alecensa (alectinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1269A	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK G1269A	lung non-small cell carcinoma	resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK demonstrated stable disease when treated with Xalkori (crizotinib), but then progressed, and was found to harbor a secondary resistance mutation, ALK G1269A (PMID: 22235099).	22235099
EML4 - ALK ALK G1269A	lung non-small cell carcinoma	resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1269A was identified in the post-progression biopsy of a patient with non-small cell lung cancer harboring EML4-ALK who was treated with Xalkori (crizotinib) (PMID: 33166721).	33166721
EML4 - ALK ALK G1269A	lung non-small cell carcinoma	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, human lung cancer cell lines expressing ALK G1269A in the context of EML4-ALK demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 24675041).	24675041
EML4 - ALK ALK G1269A	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1269A was identified at progression on Xalkori (crizotinib) in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 38360931).	38360931
EML4 - ALK ALK G1269A	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK G1269A was identified at progression on Xalkori (crizotinib) in two patients with lung adenocarcinoma harboring EML4-ALK (PMID: 34058070).	34058070
EML4 - ALK ALK G1269A	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22235099).	22235099
EML4 - ALK ALK G1269A	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1269A	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1269A	lung non-small cell carcinoma	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, human lung cancer cell lines harboring EML4-ALK with ALK G1269A demonstrated sensitivity to Zykadia (ceritinib) in culture (PMID: 24675041).	24675041
EML4 - ALK ALK G1269A	lung adenocarcinoma	sensitive	Ceritinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) treatment inhibited viability of patient-derived organoids of lung adenocarcinoma harboring EML4-ALK and ALK G1269A in culture and resulted in tumor shrinkage in a patient-derived xenograft (PDX) model (PMID: 38360931).	38360931
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859).	27009859
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 25727400).	25727400
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	lung non-small cell carcinoma	sensitive	Lorlatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and growth of non-small cell lung cancer (NSCLC) cells over expressing ALK G1269A in the context of EML4-ALK in culture and in cell line xenograft models, as well as inhibited growth of patient derived NSCLC cells harboring EML4-ALK ALK G1269A in culture (PMID: 26144315).	26144315
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	Advanced Solid Tumor	resistant	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, a cell line expressing EML4-ALK with ALK G1269A was resistant to Ensartinib (X-396) in culture (PMID: 31446141).	31446141
EML4 - ALK ALK G1269A	Advanced Solid Tumor	predicted - resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated a decreased response when treated with Rozlytrek (entrectinib) compared to cells expressing wild-type EML4-ALK (PMID: 26939704).	26939704
EML4 - ALK ALK G1269A	Advanced Solid Tumor	predicted - resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	AZD3463	Preclinical - Cell culture	Actionable	In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859).	27009859
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 35421578).	35421578
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1269A in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK G1269A	Advanced Solid Tumor	predicted - sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 moderately inhibited viability of cells expressing EML4-ALK and ALK G1269A in culture (PMID: 39269178).	39269178
EML4 - ALK ALK G1269A	Advanced Solid Tumor	sensitive	XMU-MP-5	Preclinical - Cell culture	Actionable	In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 34845836).	34845836
EML4 - ALK ALK I1171T	Advanced Solid Tumor	predicted - sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing ALK I1171T in the context of EML4-ALK but to a lesser degree than cells expressing EML4-ALK in culture (PMID: 25228534).	25228534
EML4 - ALK ALK I1171T	Advanced Solid Tumor	predicted - sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	Advanced Solid Tumor	predicted - sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 35421578).	35421578
EML4 - ALK ALK I1171T	Advanced Solid Tumor	resistant	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to ASP3026 treatment in culture (PMID: 25228534).	25228534
EML4 - ALK ALK I1171T	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T demonstrated sensitivity to Alecensa (alectinib) treatment in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171T	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534).	25228534
EML4 - ALK ALK I1171T	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	lung non-small cell carcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response with Xalkori (crizotinib) treatment, but after eight months showed progression, and was found to harbor a secondary resistance mutation, ALK I1171T (PMID: 25393798).	25393798
EML4 - ALK ALK I1171T	Advanced Solid Tumor	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171T	Advanced Solid Tumor	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK I1171T in culture (PMID: 25228534).	25228534
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	lung non-small cell carcinoma	sensitive	Lorlatinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and cell growth in patient derived non-small cell lung cancer cells harboring ALK I1171T in the context of EML4-ALK in culture (PMID: 26144315).	26144315
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171T	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, TAE684 inhibited growth of a transformed cell line expressing EML4-ALK ALK I1171T in culture (PMID: 25228534).	25228534
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 35421578).	35421578
EML4 - ALK ALK I1171T	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171T in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171T	Advanced Solid Tumor	predicted - sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 moderately inhibited viability of cells expressing EML4-ALK and ALK I1171T in culture (PMID: 39269178).	39269178
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	XMU-MP-5	Preclinical - Cell culture	Actionable	In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 34845836).	34845836
EML4 - ALK ALK I1171T	Advanced Solid Tumor	sensitive	APG-2449	Preclinical - Cell culture	Actionable	In a preclinical study, APG-2449 inhibited proliferation of cells expressing EML4-ALK with ALK I1171T in culture (PMID: 35820889).	35820889
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534).	25228534
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of a cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 31446141).	31446141
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640).	33627640
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 35421578).	35421578
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, ASP3026 inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534).	25228534
EML4 - ALK ALK V1180L	lung non-small cell carcinoma	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, a human non-small cell lung cancer cell line harboring EML4-ALK with ALK V1180L was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534).	25228534
EML4 - ALK ALK V1180L	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK V1180L was identified at progression on Alecensa (alectinib) in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 34058070).	34058070
EML4 - ALK ALK V1180L	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK V1180L was identified in the post-progression biopsy of a patient with metastatic lung adenocarcinoma harboring EML4-ALK who progressed on treatment with Alecensa (alectinib) (PMID: 37907052).	37907052
EML4 - ALK ALK V1180L	large cell neuroendocrine carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK V1180L was identified on post-progression biopsy in a patient with large cell neuroendocrine lung carcinoma harboring EML4-ALK (e20:e20), who previously responded to Alecensa (alectinib) treatment (PMID: 36207130).	36207130
EML4 - ALK ALK V1180L	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing EML4-ALK with ALK V1180L was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534).	25228534
EML4 - ALK ALK V1180L	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK V1180L were resistant to Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK V1180L	lung non-small cell carcinoma	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, a human non-small cell lung cancer cell line harboring ALK V1180L in the context of EML4-ALK was resistant to Xalkori (crizotinib) treatment in culture (PMID: 25228534).	25228534
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640).	33627640
EML4 - ALK ALK V1180L	lung adenocarcinoma	predicted - sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a retrospective analysis, Zykadia (ceritinib) treatment resulted in a partial response with a progression-free survival of 7.3 months, overall survival of 26.3 months, and a duration of treatment of 8.2 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) with ALK V1180L (PMID: 39500140).	39500140
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534).	25228534
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of a cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 31446141).	31446141
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640).	33627640
EML4 - ALK ALK V1180L	lung cancer	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response lasting 20 months in a patient with lung cancer harboring EML4-ALK with ALK V1180L (PMID: 39363320; NCT02517892).	39363320
EML4 - ALK ALK V1180L	lung non-small cell carcinoma	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis of non-small cell lung carcinoma cells harboring ALK V1180L in the context of EML4-ALK in culture (PMID: 26144315).	26144315
EML4 - ALK ALK V1180L	lung small cell carcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in tumor shrinkage after 5 months, with decrease in the size of intracranial and pulmonary lesions, in a patient with transformed small cell lung cancer from lung adenocarcinoma harboring EML4-ALK and ALK V1180L (PMID: 37907052).	37907052
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 31446141).	31446141
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640).	33627640
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 31446141).	31446141
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640).	33627640
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, TAE684 inhibited growth of a transformed cell line expressing ALK V1180L in the context of EML4-ALK in culture (PMID: 25228534).	25228534
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640).	33627640
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 35421578).	35421578
EML4 - ALK ALK V1180L	Advanced Solid Tumor	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK and ALK V1180L in culture (PMID: 39269178).	39269178
EML4 - ALK ALK I1171S	lung adenocarcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response with regression of the liver lesions and disease control in the intrathoracic and brain metastases lasting at least 9 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e19) and ALK I1171S (PMID: 29981924).	29981924
EML4 - ALK ALK I1171S	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171S	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 31943796).	31943796
EML4 - ALK ALK I1171S	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 35421578).	35421578
EML4 - ALK ALK I1171S	Advanced Solid Tumor	conflicting	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alunbrig (brigatinib)-mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK I1171S	Advanced Solid Tumor	resistant	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK I1171S	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer initially responded to Alecensa (alectinib), but progressed with the emergence of a secondary ALK I1171S mutation (PMID: 25393796).	25393796
EML4 - ALK ALK I1171S	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK I1171S was identified on post-progression biopsy in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e19) who previously responded to Alecensa (alectinib) treatment (PMID: 29981924).	29981924
EML4 - ALK ALK I1171S	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK I1171S	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK I1171S was identified on post-progression biopsy in a patient with metastatic lung adenocarcinoma harboring EML4-ALK, who previously responded to Xalkori (crizotinib) (PMID: 36324562).	36324562
EML4 - ALK ALK I1171S	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK I1171S	lung adenocarcinoma	predicted - sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, Zykadia (ceritinib) treatment resulted in tumor shrinkage with a progression-free survival of at least 8 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and ALK I1171S (PMID: 36324562).	36324562
EML4 - ALK ALK I1171S	Advanced Solid Tumor	conflicting	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Zykadia (ceritinib)-mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK I1171S	Advanced Solid Tumor	conflicting	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171S	Advanced Solid Tumor	conflicting	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S	Advanced Solid Tumor	conflicting	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 31943796).	31943796
EML4 - ALK ALK I1171S	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171S demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK I1171S	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S	Advanced Solid Tumor	resistant	AZD3463	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to AZD3463 mediated growth inhibition in culture (PMID: 27009859).	27009859
EML4 - ALK ALK I1171S	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 35421578).	35421578
EML4 - ALK ALK I1171S	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK I1171S in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340).	34158340
EML4 - ALK ALK I1171S	Advanced Solid Tumor	predicted - sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 moderately inhibited viability of cells expressing EML4-ALK and ALK I1171S in culture (PMID: 39269178).	39269178
EML4 - ALK ALK T1151M	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859).	27009859
EML4 - ALK ALK T1151M	Advanced Solid Tumor	resistant	ASP3026	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cell lines harboring EML4-ALK with ALK T1151M were resistant to ASP3026 in culture (PMID: 27009859).	27009859
EML4 - ALK ALK T1151M	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859).	27009859
EML4 - ALK ALK T1151M	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859).	27009859
EML4 - ALK ALK T1151M	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cell lines harboring EML4-ALK with ALK T1151M were resistant to Zykadia (ceritinib) in culture (PMID: 27009859).	27009859
EML4 - ALK ALK T1151M	Advanced Solid Tumor	sensitive	AZD3463	Preclinical - Cell culture	Actionable	In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859).	27009859
EML4 - ALK ALK T1151M	Advanced Solid Tumor	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK and ALK T1151M in culture (PMID: 39269178).	39269178
EML4 - ALK ALK E1210K	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK E1210K	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, a cell line expressing EML4-ALK with ALK E1210K was resistant to Alecensa (alectinib) in culture (PMID: 31446141).	31446141
EML4 - ALK ALK E1210K	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Alecensa (alectinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK E1210K	lung non-small cell carcinoma	resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical study, a patient with non-small cell lung carcinoma harboring EML4-ALK progressed on treatment with Xalkori (crizotinib) and was subsequently found to harbor a secondary resistance mutation, ALK E1210K (PMID: 29636358).	29636358
EML4 - ALK ALK E1210K	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK E1210K	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK E1210K in culture (PMID: 31446141).	31446141
EML4 - ALK ALK E1210K	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK E1210K	Advanced Solid Tumor	resistant	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, a cell line expressing EML4-ALK with ALK E1210K was resistant to Ensartinib (X-396) in culture (PMID: 31446141).	31446141
EML4 - ALK ALK E1210K	Advanced Solid Tumor	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK and ALK E1210K in culture (PMID: 39269178).	39269178
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with L1198F in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F demonstrated sensitivity to Alecensa (alectinib) treatment in culture (PMID: 27432227).	27432227
EML4 - ALK ALK L1198F	Advanced Solid Tumor	conflicting	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing L1198F in the context of EML4-ALK in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	conflicting	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, a cell line expressing EML4-ALK with ALK L1198F was resistant to Zykadia (ceritinib) in culture (PMID: 31446141).	31446141
EML4 - ALK ALK L1198F	Advanced Solid Tumor	conflicting	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F	Advanced Solid Tumor	conflicting	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	predicted - sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	predicted - sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F had reduced sensitivity to growth inhibition mediated by Lorbrena (lorlatinib) in comparison to wild-type EML4-ALK in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK L1198F in culture (PMID: 31446141).	31446141
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F in the context of EML4-ALK in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1198F	Advanced Solid Tumor	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK and ALK L1198F in culture (PMID: 39269178).	39269178
EML4 - ALK ALK L1198F ALK G1269A	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A and L1198F in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1269A	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1269A	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were re-sensitized and became modestly sensitive to Xalkori (crizotinib) with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1269A	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK L1198F ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910).	26698910
EML4 - ALK ALK G1202del	Advanced Solid Tumor	decreased response	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated a decreased response to treatment with Alunbrig (brigatinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK G1202del	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, a cell line expressing EML4-ALK with ALK G1202del was resistant to Alecensa (alectinib) in culture (PMID: 31446141).	31446141
EML4 - ALK ALK G1202del	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated moderate resistance to treatment with Alecensa (alectinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK G1202del	Advanced Solid Tumor	decreased response	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK G1202del	Advanced Solid Tumor	decreased response	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated a decreased response to treatment with Zykadia (ceritinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK G1202del	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK G1202del in culture (PMID: 31446141).	31446141
EML4 - ALK ALK G1202del	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK G1202del	Advanced Solid Tumor	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK and ALK G1202del in culture (PMID: 39269178).	39269178
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alecensa (alectinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e19:e20) who responded to Xalkori (crizotinib) treatment was found to have acquired ALK D1203N upon disease progression (PMID: 38149055).	38149055
EML4 - ALK ALK D1203N	Advanced Solid Tumor	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N	Advanced Solid Tumor	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response and progression-free survival of 19 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e19:e20) and ALK D1203N (PMID: 38149055).	38149055
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	Advanced Solid Tumor	resistant	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells overexpressing ALK D1203N in the context of EML4-ALK were resistant to TAE684 in culture (PMID: 21948233).	21948233
EML4 - ALK ALK D1203N	Advanced Solid Tumor	predicted - resistant	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N	Advanced Solid Tumor	predicted - sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 moderately inhibited viability of cells expressing EML4-ALK and ALK D1203N in culture (PMID: 39269178).	39269178
EML4 - ALK ALK D1203N ALK E1210K	Advanced Solid Tumor	decreased response	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N ALK E1210K	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N ALK E1210K	Advanced Solid Tumor	decreased response	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N ALK E1210K	Advanced Solid Tumor	decreased response	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227).	27432227
EML4 - ALK ALK D1203N ALK E1210K	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227).	27432227
EML4 - ALK ALK S1206F	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK S1206F in the context of EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK S1206F	lung adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in clinical improvement within one week of therapy, a 30.3% decrease in target lesion and a partial response after 2 months, and an ongoing response after 4 months in a patient with lung adenocarcinoma harboring de novo EML4-ALK-(E5;A20) and ALK S1206F (PMID: 27565908).	27565908
EML4 - ALK ALK S1206F	lung non-small cell carcinoma	predicted - resistant	Ensartinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK S1206F, along with EML4-ALK (v3), was identified in plasma cell-free DNA in a patient with non-small cell lung cancer harboring EML4-ALK (v5) who progressed on Ensartinib (X-396) treatment (PMID: 31446141).	31446141
EML4 - ALK ALK S1206F	Advanced Solid Tumor	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK and ALK S1206F in culture (PMID: 39269178).	39269178
EML4 - ALK ALK L1152P	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1152P in the context of EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK L1152P	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152P in culture (PMID: 35421578).	35421578
EML4 - ALK ALK L1152P	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1152P in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK L1152P	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152P demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 24675041).	24675041
EML4 - ALK ALK L1152P	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK L1152P in the context of EML4-ALK demonstrated reduced sensitivity to Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853).	27780853
EML4 - ALK ALK L1152P	Advanced Solid Tumor	sensitive	Iruplinalkib	Preclinical - Cell culture	Actionable	In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152P in culture (PMID: 35421578).	35421578
EML4 - ALK ALK L1198P	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells overexpressing ALK L1198P in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 21948233).	21948233
EML4 - ALK ALK L1198P	Advanced Solid Tumor	resistant	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells overexpressing ALK L1198P in the context of EML4-ALK were resistant to TAE684 in culture (PMID: 21948233).	21948233
EML4 - ALK ALK I1171T ALK G1269A	lung non-small cell carcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a Phase II trial (ALTA-2), Alunbrig (brigatinib) therapy resulted in a partial response lasting at least 7.4 months in a patient with advanced non-small cell lung cancer harboring EML4-ALK, ALK G1269A, and ALK I1171T who previously progressed on Alecensa (alectinib) therapy (PMID: 36096442; NCT05421936).	36096442
EML4 - ALK ALK I1171T ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534).	29650534
EML4 - ALK ALK S1206C ALK E1210K	lung non-small cell carcinoma	resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK E1210K eventually progressed on treatment with Alunbrig (brigatinib) and was subsequently found to have acquired another resistance mutation, ALK S1206C in cis (PMID: 29636358).	29636358
EML4 - ALK FGFR1 amp	lung non-small cell carcinoma	predicted - resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK treated with Alunbrig (brigatinib) responded, but eventually progressed, and was subsequently found to harbor a presumed resistance alteration, FGFR1 amplification (PMID: 29636358).	29636358
EML4 - ALK HRAS amp	lung non-small cell carcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor a presumed resistance alteration, HRAS amplification (PMID: 29636358).	29636358
EML4 - ALK ALK E1303K	lung non-small cell carcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical study, a patient with non-small cell lung cancer harboring EML4-ALK and ALK E1303K developed progressive disease 7 days after Xalkori (crizotinib) treatment (PMID: 29978950).	29978950
EML4 - ALK ALK L1256F	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1256F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1256F	lung adenocarcinoma	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited Alk kinase activity and proliferation of lung adenocarcinoma cells expressing ALK L1256F in the context of EML4-ALK in cell culture (PMID: 30662002).	30662002
EML4 - ALK ALK L1256F	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1256F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1256F	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1256F	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1256F	lung adenocarcinoma	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) did not inhibit Alk kinase activity or proliferation of lung adenocarcinoma cells expressing ALK L1256F in the context of EML4-ALK in cell culture (PMID: 30662002).	30662002
EML4 - ALK ALK L1256F	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1256F	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1256F	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1256F in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S and G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A in culture (PMID: 31943796).	31943796
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Alecensa (alectinib) treatment in culture (PMID: 31943796).	31943796
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Xalkori (crizotinib) treatment in culture (PMID: 31943796).	31943796
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S and G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A in culture (PMID: 31943796).	31943796
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Lorbrena (lorlatinib) treatment in culture (PMID: 31943796).	31943796
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK I1171S ALK G1269A	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S and G1269A in culture (PMID: 33627640).	33627640
EML4 - ALK ALK G1269S	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1269S in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 21948233).	21948233
EML4 - ALK ALK G1269S	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, transformed cells expressing ALK G1269S in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture and in cell line xenograft models (PMID: 22034911).	22034911
EML4 - ALK ALK G1269S	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK G1269S in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340).	34158340
EML4 - ALK ALK L1196Q	lung non-small cell carcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and an acquired ALK L1196Q who progressed on prior Alecensa (alectinib) treatment, the response was ongoing after 17 months of treatment (PMID: 33209633).	33209633
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196Q	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EML4-ALK demonstrated disease progression following a 15-month partial response to Alecensa (alectinib) treatment, and was found to have acquired ALK L1196Q (PMID: 33209633).	33209633
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q demonstrated resistance to Alecensa (alectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q were resistant to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196Q	lung non-small cell carcinoma	predicted - resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196Q was identified in the post-progression biopsy of a patient with non-small cell lung cancer harboring EML4-ALK who was treated with Zykadia (ceritinib) (PMID: 33166721).	33166721
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640).	33627640
EML4 - ALK ALK L1196Q	Advanced Solid Tumor	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK and ALK L1196Q in culture (PMID: 39269178).	39269178
EML4 - ALK ALK T1151K	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640).	33627640
EML4 - ALK ALK T1151K	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640).	33627640
EML4 - ALK ALK T1151K	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK T1151K was identified in the post-progression biopsy of a patient with lung adenocarcinoma harboring EML4-ALK after Xalkori (crizotinib) and Zykadia (ceritinib) therapies (PMID: 28676215).	28676215
EML4 - ALK ALK T1151K	Advanced Solid Tumor	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK T1151K demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK T1151K	lung adenocarcinoma	predicted - resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK T1151K was identified in the post-progression biopsy of a patient with lung adenocarcinoma harboring EML4-ALK after Xalkori (crizotinib) and Zykadia (ceritinib) therapies (PMID: 28676215).	28676215
EML4 - ALK ALK T1151K	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640).	33627640
EML4 - ALK ALK T1151K	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640).	33627640
EML4 - ALK ALK T1151K	Advanced Solid Tumor	sensitive	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640).	33627640
EML4 - ALK ALK T1151K	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1245V	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1245V	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1245V	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1245V	Advanced Solid Tumor	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1245V	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1245V	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK F1245V were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK F1245V	Advanced Solid Tumor	sensitive	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	predicted - resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	resistant	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640).	33627640
EML4 - ALK ALK D1203N ALK F1245V	Advanced Solid Tumor	predicted - resistant	Gilteritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640).	33627640
EML4 - ALK TP53 Q331*	lung non-small cell carcinoma	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 Q331* were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33310890).	33310890
EML4 - ALK TP53 Q331*	lung non-small cell carcinoma	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 Q331* were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33310890).	33310890
EML4 - ALK TP53 Q331*	lung non-small cell carcinoma	sensitive	Alectinib + Ixazomib	Preclinical - Cell culture	Actionable	In a preclinical study, the combination therapy of Alecensa (alectinib) and Ninlaro (ixazomib) inhibited the proliferation of non-small cell lung cancer cells harboring EML4-ALK and TP53 Q331* in culture (PMID: 33310890).	33310890
EML4 - ALK TP53 V274fs	lung non-small cell carcinoma	resistant	Alectinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 V274* were resistant to treatment with Alecensa (alectinib), demonstrating cell growth in culture and tumor growth in cell line xenograft models (PMID: 33310890).	33310890
EML4 - ALK TP53 V274fs	lung non-small cell carcinoma	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 V274fs were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33310890).	33310890
EML4 - ALK TP53 V274fs	lung non-small cell carcinoma	sensitive	Alectinib + Ixazomib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination therapy of Alecensa (alectinib) and Ninlaro (ixazomib) inhibited the proliferation of non-small cell lung cancer cells harboring EML4-ALK and TP53 Q331* in culture and resulted in tumor regression in cell line xenograft models, with 3/8 achieving complete tumor regression (PMID: 33310890).	33310890
EML4 - ALK ALK S1206R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, transformed cells expressing ALK S1206R in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture and in cell line xenograft models (PMID: 22034911).	22034911
EML4 - ALK ALK Q1188_L1190del	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in significant metabolic response and stable disease lasting 11 months in an EML4-ALK-positive lung adenocarcinoma patient harboring ALK Q1188_L1190del who had previously progressed on Xalkori (crizotinib) and Zykadia (ceritinib) treatment (PMID: 33887694).	33887694
EML4 - ALK ALK G1202K	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, fourth-line Lorbrena (lorlatinib) treatment resulted in symptom improvement and response in lung disease with a progression-free survival lasting 4 months in an EML4-ALK positive a patient with lung adenocarcinoma patient harboring EML4-ALK and an acquired ALK G1202K, who had previously progressed on Xalkori (crizotinib) and Alecensa (alectinib) treatment (PMID: 33790576).	33790576
EML4 - ALK ALK A1200_G1201delinsW	lung adenocarcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK who developed resistance to Alecensa (alectinib) following acquisition of ALK A1200_G1201delinsW demonstrated symptom improvement and stable disease for 4 months with Alunbrig (brigatinib) treatment (PMID: 34548910).	34548910
EML4 - ALK ALK A1200_G1201delinsW	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, post treatment biopsy analysis of a lung adenocarcinoma patient initially harboring EML4-ALK who developed progressive disease after 20 months of Alecensa (alectinib) treatment revealed acquisition of ALK A1200_G1201delinsW (PMID: 34548910).	34548910
ARID2 - ALK EML4 - ALK	lung adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in stable disease for 12 months in a lung adenocarcinoma patient harboring two ALK fusions, EML4-ALK (e20:e20) and ARID2-ALK (e12:e23) (PMID: 35144623).	35144623
EML4 - ALK ALK L1319V	colon adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with colon adenocarcinoma harboring EML4-ALK developed progressive disease after 8 months of Alecensa (alectinib) treatment, acquisition of ALK L1319V, KRAS amplification, KRAS Q61H, and NF1 Q20* were identified in post-progression biopsies (PMID: 33776709).	33776709
EML4 - ALK ALK G1202L	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, treatment with Lorbrena (lorlatinib) resulted in stable disease with a progression-free survival of 9 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) and ALK G1202L, which was acquired after prior ALK inhibitor therapy (PMID: 33380260).	33380260
EML4 - ALK BRAF V600E	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response in the metastatic lung, liver, and brain lesions and a partial response in the lymph node metastases in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20) and BRAF V600E, with a progression-free survival of at least 26 months (PMID: 36221356).	36221356
EML4 - ALK BRAF V600E	lung adenocarcinoma	no benefit	Dabrafenib + Trametinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e13:e20) and BRAF V600E developed progressive disease after 3 months of Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment (PMID: 36221356).	36221356
EML4 - ALK ALK E1129V	lung non-small cell carcinoma	predicted - sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a Phase I trial, Zykadia (ceritinib) treatment resulted in a partial response with a progression-free survival lasting at least 400 days in a patient with non-small cell lung cancer harboring EML4-ALK (e6:e20) and ALK E1129V (PMID: 34890832; NCT01283516).	34890832
EML4 - ALK BRAF A598_T599insV	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK progressed after an initial response to Alecensa (alectinib) and was found to have acquired BRAF A598_T599insV (PMID: 36419902).	36419902
EML4 - ALK ALK V1180Y	lung non-small cell carcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a Phase II trial (ALTA-2), Alunbrig (brigatinib) therapy resulted in a partial response, with a progression-free survival of 7.4 months, in a patient with advanced non-small cell lung cancer harboring EML4-ALK and ALK V1180Y who previously progressed on Alecensa (alectinib) therapy (PMID: 36096442; NCT05421936).	36096442
EML4 - ALK IDH2 R140Q	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, IDH2 R140Q was identified at progression on Alecensa (alectinib) in a patient with non-small cell lung cancer harboring EML4-ALK (PMID: 34058070).	34058070
EML4 - ALK ALK G1123S	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alunbrig (brigatinib) inhibited viability of a cell line expressing EML4-ALK with ALK G1123S in culture (PMID: 31446141).	31446141
EML4 - ALK ALK G1123S	Advanced Solid Tumor	sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of a cell line expressing EML4-ALK with ALK G1123S in culture (PMID: 31446141).	31446141
EML4 - ALK ALK G1123S	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited viability of a cell line expressing EML4-ALK with ALK G1123S in culture (PMID: 31446141).	31446141
EML4 - ALK ALK G1123S	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, a cell line expressing EML4-ALK with ALK G1123S was resistant to Zykadia (ceritinib) in culture (PMID: 31446141).	31446141
EML4 - ALK ALK G1123S	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK G1123S in culture (PMID: 31446141).	31446141
EML4 - ALK ALK G1123S	Advanced Solid Tumor	sensitive	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK G1123S in culture (PMID: 31446141).	31446141
EML4 - ALK ALK L1196P	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Alunbrig (brigatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196P	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Alecensa (alectinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196P	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Xalkori (crizotinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196P	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Zykadia (ceritinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196P	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196P was identified in the post-progression circulating tumor DNA of a patient with relapsed non-small cell lung cancer harboring EML4-ALK treated with Lorbrena (lorlatinib), and in a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196P	Advanced Solid Tumor	resistant	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Augtyro (repotrectinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196P	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to TPX-0131 in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1198R	Advanced Solid Tumor	predicted - resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1198R were moderately resistant to Alunbrig (brigatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1198R	Advanced Solid Tumor	predicted - resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1198R were moderately resistant to Alecensa (alectinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1198R	lung non-small cell carcinoma	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a clinical case study, ALK L1198R was identified in the post-progression circulating tumor DNA of a patient with relapsed non-small cell lung cancer harboring EML4-ALK treated with Xalkori (crizotinib), and in a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Xalkori (crizotinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1198R	Advanced Solid Tumor	predicted - resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1198R were moderately resistant to Zykadia (ceritinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1198R	Advanced Solid Tumor	predicted - resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1198R were moderately resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Alunbrig (brigatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Alecensa (alectinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Xalkori (crizotinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Zykadia (ceritinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Augtyro (repotrectinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to TPX-0131 in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1235R ALK C1237Y	lung non-small cell carcinoma	predicted - resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with relapsed non-small cell lung cancer harboring EML4-ALK developed progressive disease while on treatment with Alunbrig (brigatinib), and was found to have acquired ALK C1235R and ALK C1237Y in trans by liquid biopsy (PMID: 38448512).	38448512
EML4 - ALK ALK R1181H	lung adenocarcinoma	sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, Alunbrig (brigatinib) treatment resulted in an ongoing partial response after 12 months in a patient with lung adenocarcinoma harboring EML4-ALK and ALK R1181H, and in a preclinical study, inhibited proliferation of cells expressing EML4-ALK and ALK R1181H in culture (PMID: 38960389).	38960389
EML4 - ALK ALK R1181H	lung adenocarcinoma	predicted - resistant	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK R1181H was identified in the post-progression biopsy of a patient with lung adenocarcinoma harboring EML4-ALK who previously responded to treatment with Xalkori (crizotinib) (PMID: 38960389).	38960389
EML4 - ALK ALK R1181H	Advanced Solid Tumor	predicted - sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) inhibited proliferation of cells expressing EML4-ALK and ALK R1181H in culture (PMID: 38960389).	38960389
EML4 - ALK ALK P1094H	lung non-small cell carcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK P1094H was identified in the post-progression biopsy of a patient with non-small cell lung cancer harboring EML4-ALK who was treated with Alecensa (alectinib) (PMID: 33166721).	33166721
EML4 - ALK ALK E803Q ALK V1180L	lung adenocarcinoma	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK E803Q and V1180L were identified in post-progression biopsy in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e20), who previously achieved a partial response on Alecensa (alectinib) treatment (PMID: 39267820).	39267820
ALK F1174S	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1174S in an in vitro assay (PMID: 34158340).	34158340
ALK R1275L	neuroblastoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a Phase I/II trial, Xalkori (crizotinib) treatment was well-tolerated and resulted in stable disease in a pediatric patient with neuroblastoma harboring ALK R1275L who stayed on treatment for 4 cycles (PMID: 23598171; NCT00939770).	23598171
ALK G1269A	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing ALK G1269A was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722).	27049722
ALK G1269A	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK G1269A in culture (PMID: 27483357).	27483357
ALK G1269A	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK G1269A in an in vitro assay (PMID: 34158340).	34158340
ALK G1269A	Advanced Solid Tumor	predicted - sensitive	APG-2449	Preclinical - Biochemical	Actionable	In a preclinical study, APG-2449 inhibited the kinase activity of ALK G1269A in culture (PMID: 35820889).	35820889
ALK L1152V ALK G1269A	lung non-small cell carcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a clinical case study, Ensartinib (X-396) treatment resulted in a partial response in a patient with non-small cell lung cancer harboring ALK L1152V and ALK G1269A (PMID: 31446141).	31446141
ALK I1171T	ganglioneuroblastoma	predicted - sensitive	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, Zykadia (ceritinib) treatment resulted in a 43.6% decrease of the primary tumor after 6.5 months of treatment, and complete resolution of metastases at 21 months after initiation of treatment in a pediatric patient with ganglioneuroblastoma harboring ALK I1171T (PMID: 29907598).	29907598
ALK V1180L	lung non-small cell carcinoma	predicted - sensitive	Brigatinib	Case Reports/Case Series	Actionable	In a Phase II trial (ALTA-2), Alunbrig (brigatinib) therapy resulted in a partial response, with a progression-free survival of 11 months, in a patient with advanced non-small cell lung cancer harboring ALK V1180L who previously progressed on Alecensa (alectinib) therapy (PMID: 36096442; NCT05421936).	36096442
ALK V1180L	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK V1180L in an in vitro assay (PMID: 34158340).	34158340
ALK L1198F	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK L1198F in an in vitro assay (PMID: 34158340).	34158340
ALK S1206C ALK E1210K	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK S1206C and ALK E1210K compound mutation in an in vitro assay (PMID: 34158340).	34158340
ALK D1203N	Advanced Solid Tumor	decreased response	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, ALK D1203N demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340).	34158340
ALK D1203N ALK E1210K	Advanced Solid Tumor	decreased response	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, ALK D1203N and E1210K compound mutation demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340).	34158340
ALK Y1278S	Advanced Solid Tumor	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, a transformed cell line expressing ALK Y1278S was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722).	27049722
ALK Y1278S	neuroblastoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a partial response in a neuroblastoma patient harboring ALK Y1278S (PMID: 38787533; NCT04477681).	38787533
ALK Y1278S	Advanced Solid Tumor	sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK Y1278S in culture (PMID: 27483357).	27483357
ALK Y1278S	Advanced Solid Tumor	sensitive	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Augtyro (repotrectinib) decreased Alk phosphorylation and neurite outgrowth in cells expressing ALK Y1278S in culture (PMID: 31852910).	31852910
ALK act mut	neuroblastoma	sensitive	Lorlatinib	Phase I	Actionable	In a Phase I trial, Lorbrena (lorlatinib) treatment was well tolerated and resulted in a modified response rate of 30% (7/23) in children and 67% (10/15) in adults with neuroblastoma harboring an ALK activating mutation, including ALK F1174C, F1174L, R1275Q, or R1275L, F1245Y, F1245L, D1276_R1279delinsE, or amplification (PMID: 37012551; NCT03107988).	37012551
ALK act mut	neuroblastoma	predicted - sensitive	Navitoclax + Trametinib	Preclinical - Cell culture	Actionable	In a preclinical study, the addition of Mekinist (trametinib) sensitized neuroblastoma cell lines harboring ALK activating mutations to Navitoclax (ABT-263), resulting in reduced cell viability in culture (PMID: 36895472).	36895472
ALK act mut	neuroblastoma	predicted - sensitive	S63845 + Trametinib	Preclinical - Cell culture	Actionable	In a preclinical study, the addition of Mekinist (trametinib) sensitized a neuroblastoma cell line harboring an ALK activating mutation to S63845 (MIK655), resulting in reduced cell viability in culture (PMID: 36895472).	36895472
ALK act mut	neuroblastoma	sensitive	Cyclophosphamide + Lorlatinib + Topotecan	Phase I	Actionable	In a Phase I trial, the combination of Lorbrena (lorlatinib), Topotecan, and Cytoxan (cyclophosphamide) treatment was well tolerated and resulted in a modified response rate of 63% (5/8) in pediatric patients with neuroblastoma harboring an ALK activating mutation, including ALK F1174C, F1174L, R1275Q, or R1275L (PMID: 37012551; NCT03107988).	37012551
ALK act mut	neuroblastoma	predicted - sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NUV-655 inhibited proliferation of neuroblastoma cell lines harboring activating mutations in ALK in culture (Cancer Res (2022) 82 (12_Supplement): 3337).	detail...
ALK act mut	neuroblastoma	predicted - sensitive	Trametinib + Venetoclax	Preclinical - Cell culture	Actionable	In a preclinical study, the addition of Mekinist (trametinib) sensitized a neuroblastoma cell line harboring an ALK activating mutation to Venclexta (venetoclax), resulting in reduced cell viability in culture (PMID: 36895472).	36895472
ALK act mut TP53 wild-type	neuroblastoma	predicted - sensitive	Crizotinib + Cyclophosphamide + Topotecan	Preclinical - Cell line xenograft	Actionable	In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to delay tumor growth in xenograft models of a human neuroblastoma cell line harboring constitutively phosphorylated wild-type Alk and wild-type TP53 (PMID: 26438783).	26438783
ALK T1151M	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK T1151M in an in vitro assay (PMID: 34158340).	34158340
ALK E1210K	lung non-small cell carcinoma	predicted - resistant	Ensartinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with non-small cell lung cancer progressed on Ensartinib (X-396) treatment and was found to have acquired ALK E1210K and lost ALK L1152V and G1269A in plasma cell-free DNA (PMID: 31446141).	31446141
ALK E1210K	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK E1210K in an in vitro assay (PMID: 34158340).	34158340
ALK D1091N	neuroblastoma	predicted - sensitive	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) treatment in a neuroblastoma cell line harboring ALK D1091N resulted in decreased cell viability, inhibition of colony formation, and inhibition of Pi3k pathway signaling in culture (PMID: 28455243).	28455243
ALK D1091N	neuroblastoma	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) decreased viability of a neuroblastoma cell line harboring ALK D1091N in culture (PMID: 38032104).	38032104
ALK D1091N	neuroblastoma	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) decreased viability of a neuroblastoma cell line harboring ALK D1091N in culture (PMID: 38032104).	38032104
ALK D1091N	neuroblastoma	predicted - sensitive	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Lorbrena (lorlatinib) decreased viability of a neuroblastoma cell line harboring ALK D1091N in culture (PMID: 38032104).	38032104
ALK D1091N	neuroblastoma	sensitive	AZD3463	Preclinical - Cell culture	Actionable	In a preclinical study, AZD3463 treatment in a neuroblastoma cell line harboring ALK D1091N resulted in inhibition of colony formation, repression of Pi3k signaling, and induction of apoptosis in culture (PMID: 26786851).	26786851
ALK D1091N	neuroblastoma	predicted - sensitive	Alectinib + Doxorubicin	Preclinical - Cell culture	Actionable	In a preclinical study, Alecensa (alectinib) treatment enhanced the cytotoxic effects of Adriamycin (doxorubicin) in a neuroblastoma cell line harboring ALK D1091N, demonstrating increased apoptotic activity and decreased cell viability in culture (PMID: 28455243).	28455243
ALK D1091N	neuroblastoma	sensitive	AZD3463 + Doxorubicin	Preclinical - Cell culture	Actionable	In a preclinical study, AZD3463 treatment enhanced the cytotoxic effects of Adriamycin (doxorubicin) in a neuroblastoma cell line harboring ALK D1091N, demonstrating increased apoptotic activity and decreased cell viability in culture (PMID: 28455243).	28455243
ALK G1269S	Advanced Solid Tumor	predicted - sensitive	Conteltinib	Preclinical - Biochemical	Actionable	In a preclinical study, Conteltinib (CT-707) inhibited ALK G1269S activity in an in vitro assay (PMID: 36424628).	36424628
ALK G1269S	Advanced Solid Tumor	decreased response	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, ALK G1269S demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340).	34158340
ALK negative	anaplastic large cell lymphoma	predicted - sensitive	Brentuximab vedotin	Phase II	Actionable	In a Phase II trial (SGN-35), Adcetris (brentuximab vedotin) treatment resulted in complete remission in 57% (33/58), partial remission in 29% (17/58) of patients with relapsed or refractory systemic anaplastic large cell lymphoma, 72% (42/58) of the patients were ALK-negative (PMID: 22614995; NCT00866047).	22614995
ALK negative	leukemia	resistant	CEP-28122	Preclinical - Cell culture	Actionable	In a preclinical study, CEP-28122 did not inhibit growth of ALK-negative leukemia cells in culture (PMID: 22203728).	22203728
ALK negative	colon carcinoma	resistant	CEP-28122	Preclinical - Cell line xenograft	Actionable	In a preclinical study, CEP-28122 did not inhibit tumor growth in cell line xenograft models of ALK-negative colon carcinoma (PMID: 22203728).	22203728
ALK negative	lung non-small cell carcinoma	resistant	CEP-28122	Preclinical - Cell line xenograft	Actionable	In a preclinical study, ALK negative non-small cell lung carcinoma cells were resistant to CEP-28122 in culture and in cell line xenograft models (PMID: 22203728).	22203728
ALK negative	lymphoma	resistant	CEP-28122	Preclinical - Cell culture	Actionable	In a preclinical study, CEP-28122 did not inhibit growth of ALK-negative lymphoma cells in culture (PMID: 22203728).	22203728
ROS1 rearrange ALK neg	lung non-small cell carcinoma	sensitive	Crizotinib	Phase II	Actionable	In a Phase II trial, Xalkori (crizotinib) treatment resulted in an objective response rate of 69% (89/129), and a median duration of treatment of 7.8 months in ALK negative, ROS1 rearranged non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9022); NCT01945021).	detail...
ALK R753Q	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing ALK R753Q in culture (PMID: 34646012).	34646012
ALK G1202del	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK G1202del in an in vitro assay (PMID: 34158340).	34158340
ALK F1245I	neuroblastoma	sensitive	Alectinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Alecensa (alectinib) inhibited viability of patient-derived neuroblastoma cells harboring ALK F1245I in culture, inhibited tumor growth, and prolonged event-free survival in a patient-derived xenograft model (PMID: 37523146).	37523146
ALK F1245I	neuroblastoma	sensitive	Crizotinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited viability of patient-derived neuroblastoma cells harboring ALK F1245I in culture, inhibited tumor growth, and prolonged event-free survival in a patient-derived xenograft model (PMID: 37523146).	37523146
ALK F1245I	neuroblastoma	sensitive	Ceritinib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Zykadia (ceritinib) inhibited viability of patient-derived neuroblastoma cells harboring ALK F1245I in culture and inhibited tumor growth in a patient-derived xenograft model (PMID: 37523146).	37523146
ALK F1245I	neuroblastoma	sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical study, Lorbrena (lorlatinib) treatment resulted in a partial response in a pediatric patient with neuroblastoma harboring ALK F1245I, inhibited viability of patient-derived cells in culture, decreased tumor growth and prolonged event-free survival in a patient-derived xenograft model (PMID: 37523146; NCT03336931).	37523146
ALK L1152P	Advanced Solid Tumor	decreased response	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, ALK L1152P demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340).	34158340
ALK F1245V	neuroblastoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a complete response of marrow disease in a neuroblastoma patient harboring ALK F1245V, along with NF1 P2472fs and BRCA2 F2410fs (PMID: 37147298; NCT03107988).	37147298
ALK F1245V	neuroblastoma	predicted - sensitive	Entrectinib	Case Reports/Case Series	Actionable	In a combined analysis of 2 Phase I trials (ALKA-372-001, STARTRK-1), Rozlytrek (entrectinib) treatment resulted in a partial response that lasted 8.3 months in a patient with neuroblastoma harboring ALK F1245V, who remained on treatment for over 3.5 years due to clinical benefit (PMID: 28183697; NCT02097810).	28183697
ALK R1209Q	colon cancer	predicted - sensitive	Crizotinib + Pazopanib	Case Reports/Case Series	Actionable	In a Phase I trial, Xalkori (crizotinib) and Votrient (pazopanib) combination treatment resulted in a partial response in a patient with colon cancer harboring ALK R1209Q (PMID: 33994796; NCT01548144).	33994796
ALK over exp	neuroectodermal tumor	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in reduced volume of several metastatic tumors with disease stability lasting 4 years before treatment discontinuation, and continued for at least another 18 months off therapy, in a pediatric patient with metastatic primitive neuroectodermal tumor with ALK overexpression (PMID: 36619485).	36619485
ALK A348D	hematologic cancer	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK A348D were sensitive to treatment with Alunbrig (brigatinib) in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK A348D	hematologic cancer	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK A348D were sensitive to treatment with Xalkori (crizotinib) in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK A348D	hematologic cancer	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK A348D were sensitive to treatment with Zykadia (ceritinib) in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK A348D	hematologic cancer	sensitive	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK A348D were sensitive to treatment with TAE684 in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK A348D	hematologic cancer	sensitive	GSK1838705A	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK A348D were sensitive to treatment with GSK1838705A in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK F856S	hematologic cancer	sensitive	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK F856S were sensitive to treatment with Alunbrig (brigatinib) in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK F856S	hematologic cancer	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK F856S were sensitive to treatment with Xalkori (crizotinib) in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK F856S	Advanced Solid Tumor	sensitive	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing ALK F856S in culture (PMID: 34646012).	34646012
ALK F856S	hematologic cancer	sensitive	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK F856S were sensitive to treatment with Zykadia (ceritinib) in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK F856S	hematologic cancer	sensitive	TAE684	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK F856S were sensitive to treatment with TAE684 in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK F856S	hematologic cancer	sensitive	GSK1838705A	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells expressing ALK F856S were sensitive to treatment with GSK1838705A in culture, demonstrating decreased cell viability (PMID: 26032424).	26032424
ALK S1206R	Advanced Solid Tumor	predicted - sensitive	TPX-0131	Preclinical - Biochemical	Actionable	In a preclinical study, TPX-0131 inhibited kinase activity of ALK S1206R in an in vitro assay (PMID: 34158340).	34158340
ALK I1170N	neuroblastoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in complete remission in a neuroblastoma patient harboring ALK I1170N (PMID: 38787533; NCT04477681).	38787533
ALK F1245Y	neuroblastoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response in a patient with neuroblastoma harboring ALK F1245Y (PMID: 37147298).	37147298
ALK F1245Y HRAS G13R	neuroblastoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a Phase I trial, a neuroblastoma patient harboring ALK F1245Y developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired HRAS G13R via circulating tumor DNA (PMID: 37147298; NCT03107988).	37147298
ALK D1276_R1279delinsE	neuroblastoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in stable disease lasting for 3 years in a neuroblastoma patient harboring ALK D1276_R1279delinsE (PMID: 37147298).	37147298
ALK D1225N	lung adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring ALK D1225N (PMID: 37529699).	37529699
ALK D1225N	lung adenocarcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a clinical case study, Ensartinib (X-396) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring ALK D1225N (PMID: 37529699).	37529699
ALK del exon2-19	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response lasting at least 23 months in a patient with metastatic lung adenocarcinoma harboring a deletion of ALK exons 2-19 (PMID: 36994308).	36994308
ALK V757M	fibrosarcoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in significant tumor reduction in a patient with metastatic sclerosing epithelioid fibrosarcoma harboring ALK V757M (PMID: 37900840).	37900840
ALK del exon4-11	neuroblastoma	sensitive	Lorlatinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Lorbrena (lorlatinib) treatment inhibited proliferation of a neuroblastoma cell line harboring deletion of ALK exons 4-11 in culture and inhibited tumor growth in a cell line xenograft model (PMID: 27483357).	27483357
ALK del exon4-11	neuroblastoma	sensitive	Entrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, Rozlytrek (entrectinib) treatment inhibited ALK phosphorylation, downstream signaling, and viability of a neuroblastoma cell line harboring a deletion of ALK exons 4-11 in culture (PMID: 35085006).	35085006
ALK del exon2-17	sarcoma	sensitive	NVL-655	Preclinical - Cell culture	Actionable	In a preclinical study, NVL-655 inhibited viability of a soft tissue sarcoma cell line harboring a deletion of ALK exons 2-17 in culture (PMID: 39269178).	39269178

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