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Profile Name | EML4 - ALK ALK G1269A |
Gene Variant Detail | |
Relevant Treatment Approaches | Alectinib AZD3463 Brigatinib Ceritinib Lorlatinib |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
EML4 - ALK ALK G1269A | lung non-small cell carcinoma | sensitive | Lorlatinib | Lorlatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Lorlatinib (PF-06463922) 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 | Ceritinib | 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 | 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 | lung non-small cell carcinoma | sensitive | Ceritinib | 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 | 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 | Advanced Solid Tumor | sensitive | AZD3463 | 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 | 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 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 | Advanced Solid Tumor | conflicting | Alectinib | 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 | Advanced Solid Tumor | conflicting | Alectinib | 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 | 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 | 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 | predicted - 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 (AACR Virtual Annual Meeting II (Jun 2020), Abstract 52226). | detail... | |
EML4 - ALK ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK 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 Xalkori (crizotinib) in culture (PMID: 25727400). | 25727400 | |
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 | sensitive | Lorlatinib | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK G1269A | 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 G1269A in culture (PMID: 25727400). | 25727400 |
EML4 - ALK ALK G1269A | Advanced Solid Tumor | sensitive | Brigatinib | 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 | decreased response | 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 | lung non-small cell carcinoma | sensitive | Alectinib | 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 | 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 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
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