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Profile Name EML4 - ALK ALK L1196M ALK G1202R
Gene Variant Detail

ALK G1202R (unknown)

ALK L1196M (gain of function)

EML4 - ALK (gain of function)

Relevant Treatment Approaches

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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 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 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 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 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 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 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 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 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 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
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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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