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Profile Name EML4 - ALK ALK L1196M
Gene Variant Detail

ALK L1196M (gain of function)

EML4 - ALK (gain of function)

Relevant Treatment Approaches Brigatinib Ceritinib Ensartinib Entrectinib Lorlatinib Repotrectinib

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK ALK L1196M lung non-small cell carcinoma sensitive Ceritinib 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 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 sensitive Ensartinib 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 lung non-small cell carcinoma sensitive Lorlatinib 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 lung non-small cell carcinoma sensitive Brigatinib 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 Advanced Solid Tumor conflicting Entrectinib 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 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 sensitive Brigatinib 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 conflicting Lorlatinib 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 sensitive Ceritinib 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 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 sensitive Ceritinib 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 Repotrectinib 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 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 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 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 sensitive Ceritinib 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 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 sensitive Brigatinib 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 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 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 conflicting Lorlatinib 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 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 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 Advanced Solid Tumor conflicting Entrectinib 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 Lorlatinib 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 sensitive Ceritinib 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 Advanced Solid Tumor sensitive Brigatinib 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 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 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 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 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 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 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 Ceritinib 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 lung non-small cell carcinoma sensitive Ceritinib 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 large cell neuroendocrine carcinoma no benefit Brigatinib 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 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 non-small cell carcinoma predicted - sensitive Ensartinib 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 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