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Gene ALK
Variant G1269A
Impact List missense
Protein Effect unknown
Gene Variant Descriptions ALK G1269A lies within the protein kinase domain of the Alk protein (UniProt.org). G1269A has been demonstrated to occur as a secondary resistance mutation in the context of ALK rearrangement (PMID: 30675302, PMID: 35123209, PMID: 29872693), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Nov 2023).
Associated Drug Resistance Y
Category Variants Paths

ALK mutant ALK G1269A

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Transcript NM_004304.5
gDNA chr2:g.29209816C>G
cDNA c.3806G>C
Protein p.G1269A
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004304 chr2:g.29209816C>G c.3806G>C p.G1269A RefSeq GRCh38/hg38
NM_004304.4 chr2:g.29209816C>G c.3806G>C p.G1269A RefSeq GRCh38/hg38
NM_004304.5 chr2:g.29209816C>G c.3806G>C p.G1269A RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 sensitive 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 lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) 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 lung non-small cell carcinoma sensitive 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 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
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 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) 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 treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
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 sensitive 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 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 Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A 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 G1269A in culture, and inhibited tumor growth in xenograft models (PMID: 24887559). 24887559
EML4 - ALK ALK G1269A Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A Advanced Solid Tumor conflicting 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 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 conflicting 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 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 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 Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 35421578). 35421578
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive 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 sensitive 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 Advanced Solid Tumor predicted - resistant 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 Advanced Solid Tumor predicted - resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 26698910). 26698910
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A Advanced Solid Tumor 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 (PMID: 34158340). 34158340
EML4 - ALK ALK G1269A 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 G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive XMU-MP-5 Preclinical - Cell culture Actionable In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 34845836). 34845836
EML4 - ALK ALK G1269A 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 G1269A in culture (PMID: 35421578). 35421578
EML4 - ALK ALK G1269A lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, ALK G1269A was identified at progression on Xalkori (crizotinib) in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 38360931). 38360931
EML4 - ALK ALK G1269A lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, ALK G1269A was identified at progression on Xalkori (crizotinib) in two patients with lung adenocarcinoma harboring EML4-ALK (PMID: 34058070). 34058070
EML4 - ALK ALK G1269A Advanced Solid Tumor resistant Ensartinib Preclinical - Cell culture Actionable In a preclinical study, a cell line expressing EML4-ALK with ALK G1269A was resistant to Ensartinib (X-396) in culture (PMID: 31446141). 31446141
EML4 - ALK ALK G1269A lung adenocarcinoma sensitive Brigatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of patient-derived organoids of lung adenocarcinoma harboring EML4-ALK and ALK G1269A in culture and resulted in tumor shrinkage in a patient-derived xenograft (PDX) model (PMID: 38360931). 38360931
EML4 - ALK ALK G1269A lung adenocarcinoma sensitive Ceritinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Zykadia (ceritinib) treatment inhibited viability of patient-derived organoids of lung adenocarcinoma harboring EML4-ALK and ALK G1269A in culture and resulted in tumor shrinkage in a patient-derived xenograft (PDX) model (PMID: 38360931). 38360931
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were re-sensitized and became modestly sensitive to Xalkori (crizotinib) with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A and L1198F in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M ALK G1269A lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a patient with non-small cell lung cancer harboring EML4-ALK demonstrated a partial response when treated with Xalkori (crizotinib), however, after 6 months the patient progressed and was found to harbor two secondary resistance mutations, ALK G1269A and ALK L1196M (PMID: 23344087). 23344087
EML4 - ALK ALK L1196M ALK G1269A 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 G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK rearrange ALK T1151dup ALK G1269A lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring an ALK rearrangement demonstrated a partial response with Xalkori (crizotinib) treatment, but then progressed after 10.8 months, and was found to harbor secondary resistance mutations, ALK T1151dup and ALK G1269A (PMID: 25724526). 25724526
EML4 - ALK ALK C1156Y ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK C1156Y ALK G1269A lung adenocarcinoma unknown Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 6.9 months of therapy in a patient with lung adenocarcinoma harboring EML4-ALK, ALK C1156Y and ALK G1269A were identified in biopsies at disease progression, however, cells derived from the patient-derived xenograft (PDX) model of the patient and transformed cells expressing the compound mutation demonstrated sensitivity to Lorbrena (lorlatinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK C1156Y ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK in culture (PMID: 31585938). 31585938
EML4 - ALK ALK C1156Y ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK C1156Y ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK C1156Y ALK G1269A Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK were resistant to Rozlytrek (entrectinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK C1156Y ALK G1269A lung adenocarcinoma sensitive Lorlatinib + Saracatinib Preclinical - Patient cell culture Actionable In a preclinical study, Saracatinib (AZD0530) and Lorbrena (lorlatinib) synergistically inhibited viability of cells derived from the tumor from a patient with lung adenocarcinoma harboring EML4-ALK and acquired ALK C1156Y and G1269A compound mutation in culture (PMID: 31585938). 31585938
EML4 - ALK ALK F1174C ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK F1174C in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK I1171T ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK I1171T ALK G1269A lung non-small cell carcinoma predicted - sensitive Brigatinib Case Reports/Case Series Actionable In a Phase II trial (ALTA-2), Alunbrig (brigatinib) therapy resulted in a partial response lasting at least 7.4 months in a patient with advanced non-small cell lung cancer harboring EML4-ALK, ALK G1269A, and ALK I1171T who previously progressed on Alecensa (alectinib) therapy (PMID: 36096442; NCT05421936). 36096442
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171N was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorbrena (lorlatinib) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK G1269A 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 I1171N and G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and G1269A in culture (PMID: 33627640). 33627640
ALK rearrange ALK G1202R ALK G1269A lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R ALK G1269A developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
ALK rearrange ALK G1202R ALK L1204V ALK G1269A lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a clinical study, ALK G1269A and L1204V were identified as acquired mutations in an ALK-positive non-small cell lung cancer patient harboring ALK G1202R who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
ALK rearrange ALK D1203N ALK E1210K ALK G1269A lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a clinical study, ALK G1269A was identified as an acquired mutation in an ALK-positive non-small cell lung cancer patient harboring ALK E1210K and D1203N, who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
EML4 - ALK ALK F1174L ALK G1269A lung adenocarcinoma predicted - resistant Belizatinib Case Reports/Case Series Actionable In a clinical case study, ALK F1174L and ALK G1269A were identified as newly acquired mutations in the pleural effusion from a patient with lung adenocarcinoma harboring an acquired EML4-ALK after his disease progressed on Belizatinib (TSR-011) treatment (PMID: 28434515). 28434515
EML4 - ALK ALK F1174L ALK D1203N ALK G1269A lung adenocarcinoma predicted - resistant Ceritinib Case Reports/Case Series Actionable In a clinical case study, ALK D1203N were identified as a newly acquired mutation in the pleural effusion from a patient with lung adenocarcinoma after his disease progressed on Zykadia (ceritinib) treatment, in addition to the EML4-ALK, ALK F1174L, and ALK G1269A acquired after disease progression on Xalkori (crizotinib) and Belizatinib (TSR-011) sequentially (PMID: 28434515). 28434515
EML4 - ALK ALK T1151M ALK C1156Y ALK F1174L ALK G1202R ALK S1206F ALK G1269A lung adenocarcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 3.7 months therapy in a patient with lung adenocarcinoma harboring EML4-ALK and ALK G1202R, at disease progression, ALK F1174L in cis wth ALK G1202R was identified in biopsies, and ALK C1156Y, G1269A, S1206F, and T1151M were identified in ctDNA (PMID: 31585938). 31585938
ALK rearrange ALK G1269A lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, ALK G1269A was identified in biopsies at disease progression after 30 months of Xalkori (crizotinib) treatment in a patient with lung adenocarcinoma harboring ALK rearrangement (PMID: 31585938). 31585938
ALK rearrange ALK G1269A lung non-small cell carcinoma predicted - sensitive Lorlatinib Clinical Study Actionable In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK G1269A (n=9), with an objective response rate of 89% (8/9; 95% CI 52.0-100.0), a median duration of response not reached (NR) (95% CI 5.6-NR), and a median progression-free survival not reached (95% CI 8.2-NR) (PMID: 30892989; NCT01970865). 30892989
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Xalkori (crizotinib) treatment in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Alecensa (alectinib) treatment in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Lorbrena (lorlatinib) treatment in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S and G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S and G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A 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 I1171S and G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor predicted - sensitive NUV-655 Preclinical - Cell culture Actionable In a preclinical study, NUV-655 treatment resulted in decreased cell growth in a cell line expressing EML4-ALK fusion and ALK mutations, G1202R and G1269A, in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1468). detail...
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK G1269A were resistant to Xalkori (crizotinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK G1269A were resistant to Alecensa (alectinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1202R, ALK L1204V, and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, G1269A, and L1204V compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A, L1204V, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F, ALK G1202R, and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, G1269A, and L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A, L1198F, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Xalkori (crizotinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, S1206F, and G1269A were resistant to Zykadia (ceritinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Alecensa (alectinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Alunbrig (brigatinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). 35726063
ALK fusion ALK G1202R ALK L1204V ALK G1269A lung non-small cell carcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK L1204V and ALK G1269A were identified as acquired mutations in a non-small cell lung cancer patient harboring an ALK fusion with ALK G1202R who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). 35726063
ALK fusion ALK D1203N ALK E1210K ALK G1269A lung non-small cell carcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK G1269A was identified as an acquired mutation in a non-small cell lung cancer patient harboring an ALK fusion with ALK D1203N and ALK E1210K who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). 35726063
ALK fusion ALK G1202R ALK S1206F ALK G1269A lung non-small cell carcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK S1206F and ALK G1269A were identified as acquired mutations in a non-small cell lung cancer patient harboring an ALK fusion with ALK G1202R who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). 35726063
EML4 - ALK ALK E1129V ALK I1171T ALK F1174C ALK F1174L ALK F1174V ALK G1269A lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, ALK E1129V, F1174C, F1174L, F1174V, I1171T, and G1269A were identified in the post-progression biopsy of a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e13:e20), who previously responded to Xalkori (crizotinib) treatment (PMID: 36093526). 36093526
EML4 - ALK ALK E1129V ALK I1171T ALK F1174C ALK F1174L ALK F1174V ALK G1269A lung adenocarcinoma predicted - sensitive Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in stable disease with a progression-free survival of 10 months in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK E1129V, F1174C, F1174L, F1174V, I1171T, and G1269A (PMID: 36093526). 36093526
EML4 - ALK ALK F1174L ALK E1210K ALK G1269A lung adenocarcinoma predicted - sensitive 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 (e13:e20), ALK G1269A, ALK F1174L, and ALK E1210K (PMID: 35123209). 35123209
EML4 - ALK ALK I1171T ALK F1174L ALK L1196M ALK D1203N ALK E1210K ALK G1269A lung adenocarcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK L1196M, D1203N, and I1171T were identified at the time of progression on Lorbrena (lorlatinib) treatment in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK G1269A, ALK F1174L, and ALK E1210K (PMID: 35123209). 35123209
ALK L1152V ALK G1269A lung non-small cell carcinoma predicted - sensitive Ensartinib Case Reports/Case Series Actionable In a clinical case study, Ensartinib (X-396) treatment resulted in a partial response in a patient with non-small cell lung cancer harboring ALK L1152V and ALK G1269A (PMID: 31446141). 31446141