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Profile Name | EML4 - ALK ALK L1196M |
Gene Variant Detail | |
Relevant Treatment Approaches | Brigatinib Ceritinib Ensartinib Entrectinib Lorlatinib Repotrectinib |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
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 | 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, Ensacove (ensartinib) 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 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 | 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 | 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 | 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 | Ensartinib | Ensartinib | Preclinical | Actionable | In a preclinical study, Ensacove (ensartinib) 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 | sensitive | Deulorlatinib | Preclinical | Actionable | In a preclinical study, Deulorlatinib (TGRX-326) inhibited viability of cells expressing EML4-ALK and ALK L1196M in culture and inhibited tumor growth in a transplant model (PMID: 39551469). | 39551469 |
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