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Profile Name EML4 - ALK ALK G1202R
Gene Variant Detail

ALK G1202R (unknown)

EML4 - ALK (gain of function)

Relevant Treatment Approaches Brigatinib Lorlatinib

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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 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 lung cancer conflicting Lorlatinib 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 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 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 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 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 conflicting Brigatinib 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 lung cancer conflicting Lorlatinib 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 Advanced Solid Tumor conflicting Lorlatinib 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 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 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 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 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 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 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 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 Advanced Solid Tumor conflicting Brigatinib 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 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 lung adenocarcinoma conflicting Brigatinib 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 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 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 conflicting Lorlatinib 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 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 conflicting Brigatinib 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 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 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 EML4-ALK with ALK G1202R were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
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 adenocarcinoma conflicting Brigatinib 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 Lorlatinib 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 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 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 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 conflicting Brigatinib 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 lung squamous cell carcinoma predicted - resistant Brigatinib 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 squamous cell carcinoma predicted - sensitive Lorlatinib 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 - 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 lung adenocarcinoma predicted - sensitive Lorlatinib 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 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
EML4 - ALK ALK G1202R Advanced Solid Tumor conflicting Lorlatinib 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 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 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 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 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 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 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 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 sarcoma predicted - resistant Lorlatinib 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 adenocarcinoma predicted - sensitive Lorlatinib 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