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Profile Name ALK I1171N
Gene Variant Detail

ALK I1171N (gain of function)

Relevant Treatment Approaches ALK Inhibitor

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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 S1206Y Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK S1206Y in culture (PMID: 25727400). 25727400
EML4 - ALK ALK S1206Y Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated growth inhibition with Zykadia (ceritinib) treatment in culture (PMID: 24675041). 24675041
EML4 - ALK ALK S1206Y Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK S1206Y in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK S1206Y Advanced Solid Tumor conflicting ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated moderate resistance to Alunbrig (brigatinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK S1206Y Advanced Solid Tumor conflicting ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing S1206Y in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK S1206Y Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK S1206Y Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated moderate resistance to ASP3026 in culture (PMID: 25727400). 25727400
EML4 - ALK ALK S1206Y Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK S1206Y in culture and in xenograft models (PMID: 24887559). 24887559
EML4 - ALK ALK S1206Y Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated moderate resistance to Alecensa (alectinib) in culture (PMID: 25727400). 25727400
ALK fusion ALK S1206Y lung non-small cell carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical study, an ALK S1206Y secondary mutation in the context of an ALK fusion was associated with resistance to Xalkori (crizotinib) in a patient with non-small cell lung cancer (PMID: 22277784). 22277784
ALK rearrange ALK S1206Y lung non-small cell carcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed after 32 months, and was found to have acquired ALK S1206Y (PMID: 25724526). 25724526
ALK rearrange ALK S1206Y lung non-small cell carcinoma resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK S1206Y in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). 22277784
EML4 - ALK ALK F1174L ALK L1198V lung non-small cell carcinoma resistant ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK progressed while being treated with Alunbrig (brigatinib) and was subsequently found to harbor two resistance mutations, ALK F1174L and ALK L1198V, which were both in cis (PMID: 29636358). 29636358
EML4 - ALK ALK I1171S 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 in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Zykadia (ceritinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting ALK Inhibitor 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 in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor sensitive ALK Inhibitor WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171S in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting ALK Inhibitor 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 in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alunbrig (brigatinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171S lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer initially responded to Alecensa (alectinib), but progressed with the emergence of a secondary ALK I1171S mutation (PMID: 25393796). 25393796
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171S demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to AZD3463 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK F1174V lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK F1174V initially responded to Alecensa (alectinib), but then demonstrated progression in one of two lung nodules, which was found to harbor a secondary resistance mutation, ALK I1171S, and upon resection of the nodule the patient continued Alecensa (alectinib) treatment and achieved complete remission (PMID: 26464158). 26464158
EML4 - ALK ALK I1171S ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171S was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK I1171S ALK pos lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Ensartinib Case Reports/Case Series Actionable In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 50% (2/4) of patients with ALK-positive non-small cell lung cancer harboring ALK I1171T (n=3) or I1171S (n=1) (PMID: 31628085; NCT0321569). 31628085
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor 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 resistant ALK Inhibitor 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 ALK Inhibitor 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 sensitive ALK Inhibitor 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 ALK Inhibitor 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 resistant ALK Inhibitor 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 ALK Inhibitor 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 resistant ALK Inhibitor 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 ALK Inhibitor 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 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 I1171S ALK G1269A Advanced Solid Tumor sensitive ALK Inhibitor 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 ALK Inhibitor 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 S1206C ALK E1210K lung non-small cell carcinoma resistant ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK E1210K eventually progressed on treatment with Alunbrig (brigatinib) and was subsequently found to have acquired another resistance mutation, ALK S1206C in cis (PMID: 29636358). 29636358
ALK S1206C ALK E1210K Advanced Solid Tumor predicted - sensitive ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK S1206C and ALK E1210K compound mutation in an in vitro assay (PMID: 34158340). 34158340
ALK rearrange ALK I1171X lung non-small cell carcinoma predicted - resistant ALK Inhibitor Brigatinib Clinical Study - Cohort Actionable In a retrospective study, ALK I1171X was identified in 24% (17/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542). 31358542
ALK rearrange ALK I1171X lung non-small cell carcinoma predicted - resistant ALK Inhibitor Ensartinib Clinical Study - Cohort Actionable In a retrospective study, ALK I1171X was identified in 24% (17/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542). 31358542
ALK rearrange ALK I1171X lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Clinical Study - Cohort Actionable In a retrospective study, ALK I1171X was identified in 26% (12/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542). 31358542
ALK rearrange ALK I1171X lung non-small cell carcinoma predicted - resistant ALK Inhibitor Ceritinib Clinical Study - Cohort Actionable In a retrospective study, ALK I1171X was identified in 24% (17/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542). 31358542
ALK rearrange ALK I1171X lung non-small cell carcinoma predicted - sensitive ALK Inhibitor 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 I1171X (n=8), with an objective response rate of 75% (6/8; 95% CI 35.0-97.0), a median duration of response of 4.2 months (95% CI 2.8-4.2), and a median progression-free survival of 5.5 months (95% CI 4.1-6.9) (PMID: 30892989; NCT01970865). 30892989
ALK L1196M Advanced Solid Tumor predicted - sensitive ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK L1196M in an in vitro assay (PMID: 34158340). 34158340
ALK L1196M Advanced Solid Tumor sensitive ALK Inhibitor Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, Repotrectinib (TPX-0005) inhibited cell proliferation in transformed cell lines over expressing ALK L1196M in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
ALK L1196M neuroblastoma predicted - sensitive ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a Phase I trial, Zykadia (ceritinib) treatment resulted in a partial response with a progression-free survival over 544 days in a pediatric patient with neuroblastoma harboring ALK L1196M (PMID: 34780709; NCT01742286). 34780709
EML4 - ALK ALK L1196M lung adenocarcinoma predicted - resistant ALK Inhibitor 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 ALK Inhibitor Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorlatinib (PF-06463922) 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 conflicting ALK Inhibitor 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 conflicting ALK Inhibitor 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 conflicting ALK Inhibitor 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 ALK Inhibitor Ensartinib Preclinical Actionable In a preclinical study, Ensartinib (X-396) 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 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 ALK Inhibitor WX-0593 Preclinical - Cell culture Actionable In a preclinical study, 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 resistant ALK Inhibitor 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 resistant ALK Inhibitor 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 resistant ALK Inhibitor 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 resistant ALK Inhibitor 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 Advanced Solid Tumor conflicting ALK Inhibitor 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 ALK Inhibitor 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 resistant ALK Inhibitor 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 ALK Inhibitor Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, Repotrectinib (TPX-0005) 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 lung non-small cell carcinoma sensitive ALK Inhibitor 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 sensitive ALK Inhibitor 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 sensitive ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 lung non-small cell carcinoma sensitive ALK Inhibitor 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 Advanced Solid Tumor conflicting ALK Inhibitor 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 conflicting ALK Inhibitor 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 conflicting ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 sensitive ALK Inhibitor 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 sensitive ALK Inhibitor 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 ALK Inhibitor Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L196M 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 sensitive ALK Inhibitor 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 sensitive ALK Inhibitor 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 ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, introduction of an additional ALK mutation L1198F in transformed cells expressing ALK L1196M in the context of EML4-ALK reduced resistance to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK G1269A lung non-small cell carcinoma predicted - resistant ALK Inhibitor 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 ALK Inhibitor 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
EML4 - ALK ALK C1156Y ALK L1196M lung adenocarcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK treated on a clinical trial achieved a partial response when treated with Xalkori (crizotinib), however, after 5 months, the patient progressed and was found to harbor secondary resistance mutations, ALK C1156Y and ALK L1196M (PMID: 20979473; NCT00585195). 20979473
EML4 - ALK ALK C1156Y ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M 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
ALK rearrange ALK L1196M lung non-small cell carcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, ALK L1196M was identified in biopsies from a non-small cell lung cancer patient harboring an ALK rearrangement who developed resistance to Xalkori (crizotinib) (PMID: 22277784). 22277784
ALK rearrange ALK L1196M lung non-small cell carcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a retrospective analysis, four non-small cell lung cancer patients harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and were found to have acquired ALK L1196M (PMID: 25724526). 25724526
ALK rearrange ALK L1196M lung non-small cell carcinoma predicted - resistant ALK Inhibitor Brigatinib Clinical Study - Cohort Actionable In a retrospective study, ALK L1196M was identified in 17% (12/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542). 31358542
ALK rearrange ALK L1196M lung non-small cell carcinoma predicted - resistant ALK Inhibitor Ensartinib Clinical Study - Cohort Actionable In a retrospective study, ALK L1196M was identified in 17% (12/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542). 31358542
ALK rearrange ALK L1196M lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Clinical Study - Cohort Actionable In a retrospective study, ALK L1196M was identified in 22% (10/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542). 31358542
ALK rearrange ALK L1196M lung adenocarcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in disease progression after 4 months of therapy in a patient with ALK rearranged lung adenocarcinoma, ALK L1196M was detected in the biopsies at disease progression (PMID: 31585938). 31585938
ALK rearrange ALK L1196M lung non-small cell carcinoma predicted - resistant ALK Inhibitor Ceritinib Clinical Study - Cohort Actionable In a retrospective study, ALK L1196M was identified in 17% (12/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542). 31358542
ALK rearrange ALK L1196M lung non-small cell carcinoma predicted - sensitive ALK Inhibitor 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 L1196M (n=12), with an objective response rate of 67% (8/12; 95% CI 35.0-90.0), a median duration of response not reached (NR) (95% CI 5.2-NR), and a median progression-free survival not reached (95% CI 2.8-NR) (PMID: 30892989; NCT01970865). 30892989
EML4 - ALK ALK F1174C ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK F1174L ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174L was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK F1174V ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK I1179V ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1179V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK L1196M ALK L1256F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor 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 resistant ALK Inhibitor 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 predicted - 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 ALK Inhibitor 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 sensitive ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 resistant ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 sensitive ALK Inhibitor NUV-655 Preclinical - Cell line xenograft Actionable In a preclinical study, NUV-655 treatment resulted in decreased growth in cells expressing both EML4-ALK and ALK G1202R and L1196M in culture and resulted in tumor regression in cell-line xenograft models (Cancer Res 2021;81(13_Suppl):Abstract nr 1468). detail...
ALK rearrange ALK L1196M ALK G1202R lung non-small cell carcinoma resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R ALK L1196M developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
ALK rearrange ALK V1180L ALK L1196M ALK G1202R lung non-small cell carcinoma predicted - resistant ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R and ALK L1196M were identified at disease progression while on Alunbrig (brigatinib) treatment in liquid biopsy of a patient with ALK-positive non-small cell lung cancer also harboring an ALK V1180L (PMID: 29935304). 29935304
ALK L1196M ALK pos lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Ensartinib Case Reports/Case Series Actionable In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 25% (1/12, all partial responses) and stable disease in 67% (8/12) of patients with ALK-positive non-small cell lung cancer harboring ALK L1196M (PMID: 31628085; NCT0321569). 31628085
ALK rearrange ALK L1196M ALK D1203N lung adenocarcinoma predicted - resistant ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, Zykadia (ceritinib) treatment resulted in disease progression after 5 months of therapy in a patient with lung adenocarcinoma harboring ALK rearrangement and an acquired ALK L1196M, ALK D1203N was detected in the biopsies at disease progression (PMID: 31585938). 31585938
ALK rearrange ALK L1196M ALK D1203N lung adenocarcinoma predicted - resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring ALK rearrangement and acquired ALK L1196M, ALK D1203N mutations demonstrated primary resistance to Lorbrena (lorlatinib) treatment, resulted in immediate disease progression (PMID: 31585938). 31585938
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor predicted - resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and ALK D1203N compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1196M in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N 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 I1171N and L1196M in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1196M in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK C1156Y ALK L1196M ALK G1202R lung non-small cell carcinoma predicted - resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient with EML4-ALK, ALK G1202R, ALK L1196M, and ALK V1180L prior to Lorbrena (lorlatinib) treatment demonstrated loss of the V1180L variant and acquisition of ALK C1156Y following progression on Lorbrena (lorlatinib) (PMID: 31358542). 31358542
ALK L1196M ALK L1198F Advanced Solid Tumor predicted - sensitive ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK L1196M and ALK L1198F compound mutation in an in vitro assay (PMID: 34158340). 34158340
EML4 - ALK ALK L1196Q Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EML4-ALK demonstrated disease progression following a 15-month partial response to Alecensa (alectinib) treatment, and was found to have acquired ALK L1196Q (PMID: 33209633). 33209633
EML4 - ALK ALK L1196Q Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q 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 L1196Q in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q demonstrated resistance to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and an acquired ALK L1196Q who progressed on prior Alecensa (alectinib) treatment, the response was ongoing after 17 months of treatment (PMID: 33209633). 33209633
EML4 - ALK ALK L1196Q Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
ALK F1245C Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK F1245C in culture (PMID: 26554404). 26554404
ALK F1245C neuroblastoma resistant ALK Inhibitor Crizotinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1245C in culture, and only delayed tumor growth in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404). 26554404
ALK F1245C Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK F1245C was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK F1245C Advanced Solid Tumor predicted - sensitive ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1245C in an in vitro assay (PMID: 34158340). 34158340
ALK F1245C neuroblastoma sensitive ALK Inhibitor Lorlatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of neuroblastoma cells over expressing ALK F1245C in culture, and induced rapid and sustained complete tumor regression in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404). 26554404
ALK F1245C TP53 wild-type neuroblastoma sensitive ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Pdx Actionable In a preclinical study, Xalkori (crizotinib) worked synergistically with Topotecan and Cytoxan (cyclophosphamide), resulting in sustained tumor regression in crizotinib-resistant neuroblastoma PDX models harboring ALK F1245C and wild-type Tp53 (PMID: 26438783). 26438783
EML4 - ALK ALK F1245C lung non-small cell carcinoma sensitive ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient harboring EML4-ALK variant 3 that demonstrated resistance to treatment with Xalkori (crizotinib) after acquisition of ALK F1245C, achieved a complete radiographic response with no evidence of progression at 6 months following treatment with Zykadia (ceritinib) (PMID: 26775591). 26775591
EML4 - ALK ALK F1245C lung non-small cell carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient harboring EML4-ALK variant 3 demonstrated an initial response to treatment with Xalkori (crizotinib), but progressed after 27 months and was found to have acquired ALK F1245C (PMID: 26775591). 26775591
ALK fusion lung adenocarcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in reduction of the lung tumors in a patient with metastatic ALK-positive lung adenocarcinoma, however, there was development of new brain metastases (PMID: 35373538). 35373538
ALK fusion lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib FDA approved - Has Companion Diagnostic Actionable In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501). detail... detail... detail...
ALK fusion lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib Phase Ib/II Actionable In a phase I/II clinical trial, Alunbrig (brigatinib) was determined to be safe and efficacious in patients with advanced, ALK-fusion positive NSCLC (PMID: 24091716). 24091716
ALK fusion lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib FDA approved - Has Companion Diagnostic Actionable In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged (fusion) non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573). 28475456 detail...
ALK fusion lung non-small cell carcinoma sensitive ALK Inhibitor Crizotinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140). 25470694 detail... detail...
ALK fusion inflammatory myofibroblastic tumor sensitive ALK Inhibitor Crizotinib Phase Ib/II Actionable In a Phase Ib/II trial, treatment with Xalkori (crizotinib) resulted in an objective response rate of 86% (12/14), with complete response in 36% (5/14), in patients with inflammatory myofibroblastic tumor harboring an ALK fusion (PMID: 28787259; NCT00939770). 28787259
ALK fusion Advanced Solid Tumor sensitive ALK Inhibitor Entrectinib Phase I Actionable In a Phase I trial, Rozlytrek (entrectinib) treatment resulted in objective response in 67% (4/6) of patients with advanced solid tumors harboring rearrangement in ALK gene (AACR Apr 2016, Abstract # CT007). detail...
ALK fusion Advanced Solid Tumor sensitive ALK Inhibitor Entrectinib Phase I Actionable In a clinical study, combined analysis of 2 Phase I trials showed Rozlytrek (entrectinib) treatment resulted in an objective response rate of 57% (4/7) in patients with ALK rearranged advanced solid tumors that were treatment-naive, but no response (0/19) in patients who received prior Alk inhibitor treatments (PMID: 28183697). 28183697
ALK fusion Advanced Solid Tumor sensitive ALK Inhibitor Entrectinib Case Reports/Case Series Actionable In a Phase I/II trial (STARTRK-NG), Rozlytrek (entrectinib) treatment was safe and resulted in an overall response rate (ORR) of 57.7% (15/26, 7 complete responses) with median duration of response and progression-free survival not reached in pediatric patients with CNS or extracranial solid tumors harboring fusions in NTRK1, NTRK2, NTRK3, ROS1, or ALK, ORR was 33.3% (1/3) in patients harboring ALK fusions (PMID: 35395680; NCT02650401). 35395680
ALK fusion lung adenocarcinoma predicted - sensitive ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in reduction of the brain metastases in a patient with ALK-positive lung adenocarcinoma who had been previously treated with Alecensa (alectinib) and Xalkori (crizotinib) (PMID: 35373538). 35373538
ALK fusion anaplastic large cell lymphoma sensitive ALK Inhibitor Crizotinib FDA approved Actionable In a Phase I/II trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate (ORR) of 83% (5/6, all complete responses (CR)) at the 165 mg dose, and an ORR of 90% (18/20, 16 CR) at the 280 mg dose, in pediatric patients 1 years of age or older and young adults with relapsed or refractory ALK-positive anaplastic large cell lymphoma (PMID: 28787259; NCT00939770). 28787259 detail...
ALK fusion lung non-small cell carcinoma sensitive ALK Inhibitor Ensartinib Phase II Actionable In a Phase II trial, Ensartinib (X-396) treatment resulted in an objective response in 57% (43/75; all partial responses), and stable disease (SD) in 33% (25/75) of patients with crizotinib-refractory non-small cell lung cancer harboring an ALK fusion, with a response rate of 59% and SD rate of 31% in the 70 patients with EML4-ALK, and a response rate of 40% and SD rate of 60% in the 5 patients with non-EML4 ALK fusions (PMID: 31628085; NCT03215693). 31628085
ALK fusion Erdheim-Chester disease sensitive ALK Inhibitor Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN Guidelines). detail...
ALK fusion lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib Phase III Actionable In a Phase III trial, treatment with Alecensa (alectinib) resulted in improved progression-free survival compared to treatment with Xalkori (crizotinib) (HR=0.34) in ALK-positive non-small cell lung cancer patients (J Clin Oncol 34, 2016 (suppl; abstr 9008)). detail...
ALK fusion lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib Phase II Actionable In a Phase II trial, treatment with Alecensa (alectinib) resulted in a 49% (60/122) overall response rate in non-small cell lung cancer patients positive for an ALK fusion who had previously progressed on Xalkori (crizotinib) therapy (J Clin Oncol 33, 2015 (suppl; abstr 8008)) detail...
ALK fusion lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in non-small cell lung cancer patients harboring ALK rearrangements (PMID: 28586279; NCT02075840). detail... 28586279 detail...
ALK fusion lung non-small cell carcinoma sensitive ALK Inhibitor Ceritinib FDA approved - On Companion Diagnostic Actionable In a Phase I trial that supported FDA approval, Zykadia (ceritinib) resulted in a blinded independent review committee (BIRC)-assessed objective response rate of 44% (72/163) and a duration of response of 7.1 months in ALK-rearranged non-small cell lung cancer patients (PMID: 25754348; NCT01283516). detail... detail... 25754348
ALK fusion lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Phase I Actionable In a Phase I trial, Lorlatinib (PF-06463922) demonstrated safety and resulted in a 50% (26/52) overall response rate in patients with ALK-positive or ROS1-positive non-small cell lung cancer, including intracranial responses in patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 9009)). detail...
ALK fusion lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (Study B7461006) that supported FDA approval, Lorbrena (lorlatinib) treatment significantly improved 12-month progression-free survival rate (78% vs 39%, HR 0.28, p<0.001) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer who had no prior systemic therapy, objective response rate was 82% (57/69) with 71% achieved complete intracranial response in patients with brain metastasis (PMID: 33207094; NCT03052608). 33207094 detail... detail...
ALK fusion lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865). detail... 30413378 detail...
ALK fusion Advanced Solid Tumor predicted - sensitive ALK Inhibitor Repotrectinib Phase I Actionable In a Phase I (TRIDENT-1) trial, Repotrectinib (TPX-0005) treatment resulted in stable disease in 25% (4/16) of patient with advanced solid tumor harboring ALK fusions who completed 2 cycles of treatment (J Clin Oncol 36, 2018 (suppl; abstr 2513); NCT03093116). detail...
ALK fusion lung adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in shrinkage of the brain and spinal cord metastases in a patient with ALK-positive lung adenocarcinoma, who had been previously treated with Xalkori (crizotinib) (PMID: 35373538). 35373538
ALK fusion ALK T1151dup lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in shrinkage of the pulmonary and uterine lesions in a patient with non-small cell lung cancer and uterine metastasis harboring an ALK fusion and ALK T1151dup (reported as ALK 1151Tins), and the patient remained recurrence-free over 1 year of treatment (PMID: 34184417). 34184417
ALK fusion ALK T1151dup lung non-small cell carcinoma no benefit ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, Zykadia (ceritinib) treatment did not result in disease control in a patient with non-small cell lung cancer and uterine metastasis harboring an ALK fusion and ALK T1151dup (reported as ALK 1151Tins) whose disease progressed after prior Xalkori (crizotinib) and Alecensa (alectinib) treatments (PMID: 34184417). 34184417
ALK fusion ALK G1202R lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Phase I Actionable In a Phase I trial, treatment with Lorlatinib (PF-06463922) demonstrated safety and resulted in durable responses in patients with ALK-positive non-small cell lung cancer, including patients harboring ALK G1202R (J Clin Oncol 34, 2016 (suppl; abstr 9009)). detail...
ALK fusion ALK G1202R KIT amp lung non-small cell carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical study, an ALK G1202R secondary mutation as well as KIT amplification were identified in a patient with ALK fusion-positive non-small cell lung cancer with resistance to Xalkori (crizotinib) (PMID: 22277784). 22277784
EML4 - ALK ALK Q1188_L1190del lung adenocarcinoma predicted - sensitive ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in significant metabolic response and stable disease lasting 11 months in an EML4-ALK-positive lung adenocarcinoma patient harboring ALK Q1188_L1190del who had previously progressed on Xalkori (crizotinib) and Zykadia (ceritinib) treatment (PMID: 33887694). 33887694
ALK F1174S Advanced Solid Tumor predicted - sensitive ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1174S in an in vitro assay (PMID: 34158340). 34158340
ALK G1269A Advanced Solid Tumor predicted - sensitive ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK G1269A in an in vitro assay (PMID: 34158340). 34158340
ALK G1269A Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK G1269A was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
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 resistant ALK Inhibitor 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 resistant ALK Inhibitor 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 lung non-small cell carcinoma sensitive ALK Inhibitor 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 conflicting ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 sensitive ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 lung non-small cell carcinoma sensitive ALK Inhibitor 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 ALK Inhibitor WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 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 ALK Inhibitor 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 sensitive ALK Inhibitor 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 ALK Inhibitor 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 lung non-small cell carcinoma sensitive ALK Inhibitor 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 lung non-small cell carcinoma sensitive ALK Inhibitor 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 resistant ALK Inhibitor 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 ALK Inhibitor 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 Advanced Solid Tumor predicted - resistant ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 sensitive ALK Inhibitor 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 ALK Inhibitor 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 resistant ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 L1198F ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor 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 L1198F ALK G1269A Advanced Solid Tumor sensitive ALK Inhibitor 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 resistant ALK Inhibitor 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 ALK Inhibitor 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 sensitive ALK Inhibitor 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
ALK rearrange ALK T1151dup ALK G1269A lung non-small cell carcinoma predicted - resistant ALK Inhibitor 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 ALK Inhibitor 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 Advanced Solid Tumor resistant ALK Inhibitor 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 ALK Inhibitor 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 sensitive ALK Inhibitor 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 lung adenocarcinoma sensitive ALK Inhibitor 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 C1156Y ALK G1269A lung adenocarcinoma unknown ALK Inhibitor 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 resistant ALK Inhibitor 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 F1174C ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor 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 ALK Inhibitor 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 I1171N ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor 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 sensitive ALK Inhibitor 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 ALK Inhibitor 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
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 resistant ALK Inhibitor 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 resistant ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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
ALK rearrange ALK G1202R ALK G1269A lung non-small cell carcinoma resistant ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 non-small cell carcinoma predicted - sensitive ALK Inhibitor 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
ALK rearrange ALK G1269A lung adenocarcinoma predicted - resistant ALK Inhibitor 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
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor predicted - sensitive ALK Inhibitor 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 G1296A, in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1468). detail...
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 sensitive ALK Inhibitor 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 L1204V ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor 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 G1202R ALK L1204V ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor 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 ALK Inhibitor 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 sensitive ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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 L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor 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 sensitive ALK Inhibitor 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 ALK Inhibitor 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 L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor 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
ALK I1171N Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK I1171N was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK I1171N Advanced Solid Tumor decreased response ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, ALK I1171N demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N lung non-small cell carcinoma resistant ALK Inhibitor Crizotinib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor conflicting ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N Advanced Solid Tumor conflicting ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N demonstrated resistance to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor predicted - resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N Advanced Solid Tumor predicted - resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171N lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated tumor regression when treated with Alecensa (alectinib), but progressed seven months later, and was found to harbor a secondary resistance mutation, ALK I1171N (PMID: 25393798). 25393798
EML4 - ALK ALK I1171N lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Alecensa (alectinib) failed to inhibit growth of patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture, and did not induce tumor regression or reduce Alk phosphorylation in xenograft models (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited cell viability, decreased downstream ALK signaling, and induced apoptosis in patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N 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 in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N lung non-small cell carcinoma resistant ALK Inhibitor Entrectinib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant ALK Inhibitor TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171N in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated resistance to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive ALK Inhibitor WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171N lung non-small cell carcinoma sensitive Gilteritinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited growth of patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture, and induced tumor regression and suppressed Alk phosphorylation and downstream signaling in xenograft models (PMID: 33627640). 33627640
ALK rearrange ALK I1171N lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical study, Alunbrig (brigatinib) treatment resulted in stable disease in 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171N (PMID: 29935304). 29935304
ALK rearrange ALK I1171N lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a de novo ALK I1171N mutation was identified in the liver metastasis site and circulating DNA of a non-small cell lung cancer patient harboring an ALK rearrangement after disease progression on Alecensa (alectinib) treatment (PMID: 27565911). 27565911
ALK rearrange ALK I1171N ALK L1198F lung non-small cell carcinoma resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung cancer patient harboring ALK I1171N and L1198F in cis in the context of EML4-ALK demonstrated primary resistance to Lorlatinib (PF-06463922) (PMID: 29650534). 29650534
ALK rearrange ALK I1171N ALK D1203N lung non-small cell carcinoma resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK I1171N and D1203N developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
EML4 - ALK ALK I1171N ALK L1256F Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1256F Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1256F Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1256F Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1256F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1256F 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 L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1256F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Preclinical - Pdx Actionable In a preclinical study, Alecensa (alectinib) failed to inhibit tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I 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 F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I lung non-small cell carcinoma sensitive Gilteritinib Preclinical - Pdx Actionable In a preclinical study, Xospata (gilteritinib) induced complete tumor regression in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I, and also induced tumor regression when administered to separate PDX tumors which had demonstrated resistance to Alecensa (alectinib) or Lorbrena (lorlatinib) treatment (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I lung non-small cell carcinoma predicted - resistant ALK Inhibitor Lorlatinib Preclinical - Pdx Actionable In a preclinical study, Lorbrena (lorlatinib) failed to inhibit tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H Advanced Solid Tumor predicted - resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H 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 ALK L1198H in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H Advanced Solid Tumor predicted - resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L 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 F1174L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L Advanced Solid Tumor predicted - resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor predicted - resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F demonstrated resistance to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F 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 ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor conflicting ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor conflicting ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N ALK V1180L lung adenocarcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK, as well as IDH1 R132H, developed progressive disease after initial response to Alecensa (alectinib), and ALK I1171N and ALK V1180L were identified in the post-progression biopsy along with germline BRCA2 F2801fs (PMID: 35324529). 35324529
ALK D1203N Advanced Solid Tumor decreased response ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, ALK D1203N demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340). 34158340
EML4 - ALK ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor TAE684 Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing ALK D1203N in the context of EML4-ALK were resistant to TAE684 in culture (PMID: 21948233). 21948233
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor predicted - resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor predicted - resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor decreased response ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Lorlatinib (PF-06463922) in culture compared to cells expressing wild-type EML4-ALK (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor decreased response ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK C1156Y ALK D1203N Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK D1203N 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
ALK rearrange ALK D1203N lung non-small cell carcinoma predicted - resistant ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, ALK D1203N was identified at disease progression while on Alunbrig (brigatinib) treatment in a patient with ALK-positive non-small cell lung cancer (PMID: 29935304). 29935304
ALK rearrange ALK D1203N lung non-small cell carcinoma predicted - resistant ALK Inhibitor Lorlatinib Clinical Study - Cohort Actionable In a retrospective study, ALK D1203N was identified in 24% (7/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). 31358542
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor predicted - resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
ALK D1203N ALK E1210K Advanced Solid Tumor decreased response ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, ALK D1203N and E1210K compound mutation demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340). 34158340
ALK I1171T ganglioneuroblastoma predicted - sensitive ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, Zykadia (ceritinib) treatment resulted in a 43.6% decrease of the primary tumor after 6.5 months of treatment, and complete resolution of metastases at 21 months after initiation of treatment in a pediatric patient with ganglioneuroblastoma (PMID: 29907598). 29907598
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing ALK I1171T in the context of EML4-ALK but to a lesser degree than cells expressing EML4-ALK in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171T 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 I1171T in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171T Advanced Solid Tumor resistant ALK Inhibitor TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171T in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171T lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell growth in patient derived non-small cell lung cancer cells harboring ALK I1171T in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK I1171T Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to ASP3026 treatment in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive ALK Inhibitor 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 I1171T in culture (PMID: 34845836). 34845836
EML4 - ALK ALK I1171T Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive ALK Inhibitor WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive ALK Inhibitor TAE684 Preclinical - Cell culture Actionable In a preclinical study, TAE684 inhibited growth of a transformed cell line expressing EML4-ALK ALK I1171T in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK I1171T in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T demonstrated sensitivity to Alecensa (alectinib) treatment in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171T Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T lung non-small cell carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response with Xalkori (crizotinib) treatment, but after eight months showed progression, and was found to harbor a secondary resistance mutation, ALK I1171T (PMID: 25393798). 25393798
ALK rearrange ALK I1171T lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK I1171T was identified in the post-progression biopsy of a non-small cell lung cancer patient harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304). 29935304
ALK rearrange ALK I1171T lung adenocarcinoma resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement with ALK I1171T progressed on Alecensa (alectinib) therapy after 4 months and resistance was confirmed using cell culture with cells derived from the patient’s tumor (PMID: 25228534). 25228534
ALK rearrange ALK I1171T lung adenocarcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement with ALK I1171T progressed on Xalkori (crizotinib) therapy after 8 months and resistance was confirmed using cell culture with cells derived from the patient's tumor (PMID: 25228534). 25228534
ALK rearrange ALK I1171T lung non-small cell carcinoma predicted - resistant ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in progressive disease in a patient with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171T (PMID: 29935304). 29935304
EML4 - ALK ALK C1156Y ALK I1171T Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171T 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
ALK I1171T ALK pos lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Ensartinib Case Reports/Case Series Actionable In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 50% (2/4) of patients with ALK-positive non-small cell lung cancer harboring ALK I1171T (n=3) or I1171S (n=1) (PMID: 31628085; NCT0321569). 31628085
ALK R1275Q neuroblastoma sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK R1275Q (corresponds to R1279Q in mouse) and subsequent upregulation of Ret (PMID: 24811913). 24811913
ALK R1275Q neuroblastoma no benefit ALK Inhibitor Belizatinib Case Reports/Case Series Actionable In a Phase I trial, a neuroblastoma patient harboring ALK R1275Q did not respond to treatment with Belizatinib (TSR-011) (PMID: 31217479; NCT02048488). 31217479
ALK R1275Q Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK R1275Q in culture (PMID: 26554404). 26554404
ALK R1275Q neuroblastoma sensitive ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in human neuroblastoma cell line xenograft models harboring ALK R1275Q and wild-type TP53 (PMID: 26438783). 26438783
ALK R1275Q neuroblastoma conflicting ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, among the 12 patients harboring ALK R1275Q, 1 achieved a complete response, 2 achieved partial responses, and 2 achieved prolonged stable diseases (PMID: 33568345; NCT00939770). 33568345
ALK R1275Q neuroblastoma conflicting ALK Inhibitor Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK R1275Q in culture, and only delayed tumor growth in cell line xenograft models (PMID: 26554404). 26554404
ALK R1275Q neuroblastoma conflicting ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 29907598). 29907598
ALK R1275Q neuroblastoma conflicting ALK Inhibitor Crizotinib Preclinical Actionable In a preclinical study, Xalkori (crizotinib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK R1275Q (corresponds to R1279Q in mouse) and subsequent upregulation of Ret (PMID: 24811913). 24811913
ALK R1275Q neuroblastoma sensitive ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a Phase I trial, Zykadia (ceritinib) treatment resulted in 3 partial responses and 1 stable disease in 7 pediatric patients with neuroblastoma harboring ALK R1275Q (PMID: 34780709; NCT01742286). 34780709
ALK R1275Q neuroblastoma sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 29907598). 29907598
ALK R1275Q Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, a transformed cell line expressing ALK R1275Q was sensitive to Alunbrig (brigatinib) in culture and in cell line xenograft models, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK R1275Q neuroblastoma sensitive ALK Inhibitor CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 inhibited growth of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 22203728). 22203728
ALK R1275Q Advanced Solid Tumor predicted - sensitive ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK R1275Q in an in vitro assay (PMID: 34158340). 34158340
ALK R1275Q neuroblastoma sensitive ALK Inhibitor Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation, resulted in growth inhibition of neuroblastoma cells over expressing ALK R1275Q in culture and induced rapid and sustained complete tumor regression in cell line xenograft models (PMID: 26554404). 26554404
ALK F1174L ALK R1275Q neuroblastoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, a patient harboring both ALK F1174V and ALK R1275Q stayed on treatment for 3 cycle until disease progression (PMID: 33568345; NCT00939770). 33568345
ALK L1152V ALK pos lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Ensartinib Case Reports/Case Series Actionable In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 25% (1/4) of patients with ALK-positive non-small cell lung cancer harboring ALK L1152R (n=3) or L1152V (n=1) (PMID: 31628085; NCT0321569). 31628085
ALK D1091N neuroblastoma predicted - sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) treatment in a neuroblastoma cell line harboring ALK D1091N resulted in decreased cell viability, inhibition of colony formation, and inhibition of Pi3k pathway signaling in culture (PMID: 28455243). 28455243
ALK D1091N neuroblastoma predicted - sensitive ALK Inhibitor Alectinib + Doxorubicin Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) treatment enhanced the cytotoxic effects of Adriamycin (doxorubicin) in a neuroblastoma cell line harboring ALK D1091N, demonstrating increased apoptotic activity and decreased cell viability in culture (PMID: 28455243). 28455243
ALK D1091N neuroblastoma sensitive ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 treatment in a neuroblastoma cell line harboring ALK D1091N resulted in inhibition of colony formation, repression of Pi3k signaling, and induction of apoptosis in culture (PMID: 26786851). 26786851
ALK D1091N neuroblastoma sensitive ALK Inhibitor AZD3463 + Doxorubicin Preclinical - Cell culture Actionable In a preclinical study, AZD3463 treatment enhanced the cytotoxic effects of Adriamycin (doxorubicin) in a neuroblastoma cell line harboring ALK D1091N, demonstrating increased apoptotic activity and decreased cell viability in culture (PMID: 28455243). 28455243
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Crizotinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140). detail... 25470694 detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as first-line therapy for ALK rearranged non-small cell lung cancer (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Crizotinib Phase III Actionable In a Phase III trial (PROFILE 1014), Xalkori (crizotinib) treatment resulted in improved progression-free survival (PFS) (PFS=10.9 months, n=172) relative to chemotherapy (PFS=7.0 months, n=171) in NSCLC patients with ALK rearrangements, including patients with and without brain metastases at baseline, and improved intracranial disease rate in patients with brain metastases at baseline (PMID: 27022118; NCT01154140). 27022118
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement, or as a next-line therapy in patients with ALK-rearranged non-small cell lung cancer who have not received prior Xalkori (crizotinib) (PMID: 32169226; ESMO.org). 32169226 detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Crizotinib Phase III Actionable In a Phase III trial, Xalkori (crizotinib) treatment resulted in improved objective response (87.5%, 90/103 vs 45.6%, 47/103) and median progression free survival (11.1 vs 6.8 mo) compared to pemetrexed, cisplatin and carboplatinin combination treatment in treatment-naive ALK positive advanced non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9058); NCT01639001). detail...
ALK rearrange lung small cell carcinoma predicted - sensitive ALK Inhibitor Alectinib + Irinotecan Case Reports/Case Series Actionable In a clinical case study, treatment with the combination of Alecensa (alectinib) and Camptosar (irinotecan) resulted in a partial response with progression-free survival lasting longer than 6 months in a small cell lung carcinoma patient harboring an ALK rearrangement (PMID: 34729013). 34729013
ALK rearrange epithelioid inflammatory myofibroblastic sarcoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response lasting 44.2 months in a pediatric patient with an ALK-rearranged epithelioid inflammatory myofibroblastic tumor (PMID: 34036223). 34036223
ALK rearrange lung non-small cell carcinoma no benefit Afatinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange Advanced Solid Tumor sensitive ALK Inhibitor Belizatinib Phase Ib/II Actionable In a Phase I trial, Belizatinib (TSR-011) treatment resulted in a response in 100% (3/3) of patients with ALK-rearranged advanced solid tumors when administered at higher doses, and stable disease for 7 months or longer in 56% (5/9) of patients at a lower dose (J Clin Oncol 33, 2015 (suppl; abstr 8063)). detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in non-small cell lung cancer patients harboring ALK rearrangement (PMID: 28586279; NCT02075840). 28586279 detail... detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib Phase II Actionable In a Phase II trial, Alecensa (alectinib) treatment was effective in treating non-small cell lung cancer patients with ALK rearrangement, resulting in a 50% (61/122) objective response rate (ORR) in all patients, a 45% (43/96) ORR in Crizotinib-refractory patients, and an 83% (70/84) CNS disease control rate (PMID: 26598747). 26598747
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines as preferred first-line therapy and as subsequent therapy for patients with ALK-rearranged advanced or metastatic non-small cell lung cancer (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alecensa (alectinib), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 32169226; ESMO.org). 32169226 detail...
ALK rearrange lung non-small cell carcinoma no benefit ALK Inhibitor Crizotinib + Onalespib Phase II Actionable In a Phase II trial, Onalespib (AT13387) and Xalkori (crizotinib) combination treatment did not significantly improve median progression free survival (269 vs 266 days) or objective response rate (55.4%, 38/68 vs 45.3%, 31/68) compared to Xalkori (crizotinib) single treatment in patients with non-small cell lung carcinoma harboring either an ALK mutation or ALK rearrangement (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217). detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ensartinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Ensartinib (X-396), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ensartinib Phase Ib/II Actionable In a Phase I/II trial, Ensartinib (X-396) treatment resulted in partial response in 60% (36/60) and stable disease in 21.7 % (13/60) of patients with ALK-positive non-small cell lung cancer, with a median progression-free survival of 9.2 months, and a response rate of 80% (12/15) in crizotinib-naïve patients and 69% (20/29) in patients with prior crizotinib treatment (PMID: 29563138; NCT01625234). 29563138
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ensartinib Guideline Actionable Ensartinib (X-396) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 32169226, Version Update 15 Sept 2020; ESMO.org). 32169226 detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ensartinib Phase III Actionable In a Phase III trial, Ensartinib (X-396) treatment significantly improved progression-free survival in patients with ALK-positive non-small cell lung cancer (25.8 vs 12.7 mo, HR 0.51, p<0.001) compared to Xalkori (crizotinib), and resulted in an intracranial response rate of 63.6% (7 of 11) in patients with target brain metastases at baselinewith compared to 21.1% (4 of 19) with Xalkori (crizotinib) (PMID: 34473194; NCT02767804). 34473194
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ceritinib + Crizotinib Clinical Study - Cohort Actionable In a retrospective analysis of patients with ALK-rearrangement positive non-small cell lung cancer, the combined median progression-free survival for sequential treatment with Xalkori (crizotinib) and Zykadia (ceritinib) without intervening treatments was 17.0 months, and overall survival was 49.4 months (PMID: 25724526). 25724526
ALK rearrange lung non-small cell carcinoma no benefit ALK Inhibitor Belizatinib Phase I Actionable In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488). 31217479
ALK rearrange lung non-small cell carcinoma no benefit Erlotinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). detail...
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response lasting 40 months in a pediatric patient with an ALK-rearranged inflammatory myofibroblastic tumor (PMID: 34036223). 34036223
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a Phase I/II trial, Xalkori (crizotinib) treatment was well-tolerated and resulted in a partial response in 3 of 7 pediatric patients with ALK-rearranged inflammatory myofibroblastic tumors, and 3 of the 7 patients achieved stable disease (PMID: 23598171; NCT00939770). 23598171
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines as preferred first-line therapy and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865). detail... detail... 30413378
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (Study B7461006) that supported FDA approval, Lorbrena (lorlatinib) treatment significantly improved 12-month progression-free survival rate (78% vs 39%, HR 0.28, p<0.001) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer who had no prior systemic therapy, objective response rate was 82% (57/69) with 71% achieved complete intracranial response in patients with brain metastasis (PMID: 33207094; NCT03052608). 33207094 detail... detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Phase I Actionable In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in an objective response in 46% (19/41) of patients with non-small cell lung carcinoma harboring an ALK rearrangement (PMID: 29074098; NCT03052608). 29074098
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement who have progressed on an ALK tyrosine kinase inhibitor (PMID: 32169226; ESMO.org). detail... 32169226
ALK rearrange lung adenocarcinoma predicted - sensitive ALK Inhibitor CT-707 Phase I Actionable In a Phase I trial, Conteltinib (CT-707) demonstrated safety and preliminary efficacy, resulting in an overall response rate of 77% (10/13, 1 complete response, 9 partial responses) and a disease control rate of 85% (11/13) in patients with ALK-rearranged lung adenocarcinoma (n=12) or malignant pleural mesothelioma (n=1), median progression-free survival was 13 months in patients with lung adenocarcinoma (PMID: 32181989). 32181989
ALK rearrange anaplastic large cell lymphoma not applicable N/A Guideline Diagnostic ALK rearrangement aids in the diagnosis of anaplastic large cell lymphoma (NCCN.org). detail...
ALK rearrange anaplastic large cell lymphoma not applicable N/A Guideline Prognostic The presence of ALK rearrangement is associated with a favorable prognosis in patients with anaplastic large cell lymphoma (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Ceritinib + Ribociclib Phase Ib/II Actionable In a Phase I/II trial, Zykadia (ceritinib) and Kisqali (ribociclib) combination therapy demonstrated a manageable safety profile and resulted in an overall response rate of 37.0% (10/27; 1 complete response and 9 partial responses) with a median progression-free survival of 21.5 months in patients with advanced ALK-rearranged non-small cell lung cancer (PMID: 35298959). 35298959
ALK rearrange lung non-small cell carcinoma no benefit Pembrolizumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma no benefit Pembrolizumab Clinical Study - Cohort Actionable In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange lung adenocarcinoma predicted - sensitive ALK Inhibitor Bevacizumab + Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient with brain metastasis harboring an ALK rearrangement, who had progressed on single agent Lorbrena (lorlatinib) treatment, demonstrated a partial response when treated with a combination of Lorbrena (lorlatinib) and Avastin (bevacizumab), with a 68% decrease in tumor size in the brain and a total duration of disease control for 9.1 months (PMID: 33283131). 33283131
ALK rearrange lung non-small cell carcinoma no benefit Osimertinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange anaplastic large cell lymphoma sensitive ALK Inhibitor Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as second-line and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org). detail...
ALK rearrange anaplastic large cell lymphoma sensitive ALK Inhibitor Crizotinib FDA approved Actionable In a Phase I/II trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate (ORR) of 83% (5/6, all complete responses (CR)) at the 165 mg dose, and an ORR of 90% (18/20, 16 CR) at the 280 mg dose, in pediatric patients 1 years of age or older and young adults with relapsed or refractory ALK-positive anaplastic large cell lymphoma (PMID: 28787259; NCT00939770). 28787259 detail...
ALK rearrange lung non-squamous non-small cell carcinoma sensitive ALK Inhibitor Ceritinib Phase III Actionable In a Phase III trial, first-line treatment with Zykadia (ceritinib) resulted in an improved median progression-free survival of 16.6 months, compared to 8.1 months with chemotherapy, in patients with ALK-rearranged non-squamous non-small cell lung cancer (PMID: 28126333; NCT01828099). 28126333
ALK rearrange lung non-small cell carcinoma no benefit Nivolumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma no benefit Nivolumab Clinical Study - Cohort Actionable In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 32169226; ESMO.org). 32169226 detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ceritinib Phase II Actionable In a Phase II trial (ASCEND-2), non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement and previously treated with Xalkori (crizotinib) and chemotherapy demonstrated an overall response rate of 38.6% (54/140), a disease control rate of 77.1%, a median time to response of 1.8 months, a median duration of response of 9.7 months, and a median progression-free survival of 5.7 months when treated with Zykadia (ceritinib) (PMID: 27432917; NCT01685060). 27432917
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ceritinib FDA approved - On Companion Diagnostic Actionable In a Phase I trial that supported FDA approval, Zykadia (ceritinib) resulted in a blinded independent review committee (BIRC)-assessed objective response rate of 44% (72/163) and a duration of response of 7.1 months in ALK-rearranged non-small cell lung cancer patients (PMID: 25754348; NCT01283516). 25754348 detail... detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ceritinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated a median overall survival of 49.5 months following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Zykadia (ceritinib), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines as first-line and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma no benefit Durvalumab Clinical Study - Cohort Actionable In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Imfinzi (durvalumab), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange lung non-small cell carcinoma no benefit Durvalumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange anaplastic large cell lymphoma sensitive ALK Inhibitor Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines as second-line and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org). detail...
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Ceritinib Phase I Actionable In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 70% (7/10; 7 partial responses) and a disease control rate of 80% (8/10) in pediatric patients with inflammatory myofibroblastic tumor harboring ALK rearrangement, with median progression-free survival unreached (PMID: 34780709; NCT01742286). 34780709
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). detail...
ALK rearrange malignant pleural mesothelioma no benefit ALK Inhibitor CT-707 Case Reports/Case Series Actionable In a Phase I trial, Conteltinib (CT-707) treatment resulted in disease progression after 1 cycle in a patient with ALK-rearranged malignant pleural mesothelioma (PMID: 32181989). 32181989
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib Clinical Study Actionable In a retrospective analysis, Alunbrig (brigatinib) demonstrated limited efficacy, resulting in an objective response rate of 17% (3/18) and stable disease in 50% (9/18) of patients with Alecensa (alectinib) refractory, ALK-positive non-small cell lung cancer, with a median progression-free survival of 4.4 months (PMID: 29935304). 29935304
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 32169226; ESMO.org). 32169226 detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib Phase Ib/II Actionable In a Phase I/II trial, Alunbrig (brigatinib) treatment resulted in an objective response rate of 100% (8/8) in ALK inhibitor-naive, ALK-rearranged non-small cell lung cancer (NSCLC) patients, 72% (51/71) in Xalkori (crizotinib) treated ALK-rearranged NSCLC patients, and 83% (5/6) in ALK-rearranged NSCLC patients with CNS metastases (PMID: 27836716; NCT01449461). 27836716
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib FDA approved - Has Companion Diagnostic Actionable In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501). detail... detail... detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines as preferred first-line and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib FDA approved - Has Companion Diagnostic Actionable In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged (fusion) non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573). detail... 28475456
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alunbrig (brigatinib), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange Advanced Solid Tumor sensitive ALK Inhibitor ASP3026 Phase I Actionable In a Phase I trial, ASP3026 treatment resulted in a partial response in 50% (8/16) and stable disease in 44% (7/16) of patients with an advanced solid tumor harboring an ALK rearrangement or ALK F1174L (PMID: 26966027; NCT01284192). 26966027
ALK rearrange lung non-small cell carcinoma sensitive ALK Inhibitor WX-0593 Phase I Actionable In a Phase I trial, WX-0593 (iruplinalkib) demonstrated safety and resulted in an objective response rate (ORR) of 56.6% (56/99; all partial responses) and a disease control rate (DCR) of 83.8% (83/99), and median duration of response and median progression-free survival were not reached in non-small cell lung cancer patients with an ALK or ROS1-rearrangement, with an ORR of 58.2% (53/91; all partial responses) and DCR of 85.7% (78/91) in patients with an ALK rearrangement (PMID: 35087031; NCT03389815). 35087031
ALK rearrange lung non-small cell carcinoma predicted - sensitive ALK Inhibitor PLB1003 Phase I Actionable In a Phase Ia trial, PLB1003 demonstrated safety and preliminary efficacy, resulted in a disease control rate of 86% (12/14, 10 partial response, 2 stable disease) in patients with ALK-rearranged non-small cell lung cancer who progressed on or did not tolerate previous treatment (Journal of Thoracic Oncology, Volume 14, Issue 10, S651). detail...
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma no benefit Atezolizumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma no benefit Atezolizumab Clinical Study - Cohort Actionable In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange lung non-small cell carcinoma no benefit Gefitinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange inflammatory myofibroblastic tumor sensitive ALK Inhibitor Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). detail...
ALK rearrange anaplastic large cell lymphoma predicted - sensitive ALK Inhibitor Ceritinib Phase I Actionable In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 75% (6/8; 2 complete responses, 4 partial responses) and a disease control rate of 88% (7/8) in pediatric patients with anaplastic large cell lymphoma harboring ALK rearrangement, with median progression-free survival unreached (PMID: 34780709; NCT01742286). 34780709
ALK rearrange lung non-small cell carcinoma no benefit Ipilimumab + Nivolumab Guideline Actionable Immune checkpoint inhibitors including Keytruda (pembrolizumab), Tecentriq (atezolizumab), and the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) are not indicated for use as initial systemic therapy in non-small cell lung cancer patients harboring oncogenes, including ALK rearrangement (NCCN.org). detail...
ALK rearrange ALK C1156Y lung non-small cell carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed after 18.2 months, and was found to have acquired ALK C1156Y (PMID: 25724526). 25724526
ALK rearrange ALK C1156Y lung adenocarcinoma sensitive ALK Inhibitor 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 ALK rearrangement and an acquired ALK C1156Y in culture (PMID: 31585938). 31585938
ALK rearrange ALK C1156Y lung adenocarcinoma predicted - resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK C1156Y was identified in biopsies at disease progression after 16 months of Lorbrena (lorlatinib) treatment in a patient with lung adenocarcinoma harboring ALK rearrangement, cells derived from patient's tumor were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938). 31585938
ALK rearrange ALK C1156Y ALK L1198F lung non-small cell carcinoma resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK C1156Y ALK L1198F developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
ALK rearrange MAP2K1 K57N lung non-small cell carcinoma sensitive ALK Inhibitor Ceritinib + Selumetinib Preclinical - Patient cell culture Actionable In a preclinical study, NSCLC patient derived cells harboring an ALK rearrangement demonstrated resistance to Zykadia (ceritinib) due to the acquired mutation MAP2K1 K57N, however, sensitivity was restored to Zykadia (ceritinib) with the addition of Koselugo (selumetinib), resulting in decreased cell survival in culture and reduced tumor volume in xenograft models (PMID: 25394791). 25394791
ALK rearrange ALK G1202R lung non-small cell carcinoma sensitive ALK Inhibitor 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 G1202R or ALK G1202del (n=28), with an objective response rate of 57% (16/28; 95% CI 37.0-76.0), a median duration of response of 7 months (95% CI 6.1-24.4), and a median progression-free survival of 8.2 months (95% CI 5.6-25.6) (PMID: 30892989; NCT01970865). 30892989
ALK rearrange ALK G1202R lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Guideline Actionable Lorlatinib is included in guidelines as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK G1202R (NCCN.org). detail...
ALK rearrange ALK G1202R lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R was identified in a patient with ALK-rearranged non-small cell lung carcinoma after the disease progressed while on Xalkori (crizotinib) followed by Alecensa (alectinib) therapy (PMID: 27130468). 27130468
ALK rearrange ALK G1202R lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Clinical Study - Cohort Actionable In a retrospective study, ALK G1202R was identified in 37% (17/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542). 31358542
ALK rearrange ALK G1202R lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R was identified in a patient with ALK-rearranged non-small cell lung carcinoma after the disease progressed while on Zykadia (ceritinib) followed by Alecensa (alectinib) therapy (PMID: 28285684). 28285684
ALK rearrange ALK G1202R lung non-small cell carcinoma predicted - resistant ALK Inhibitor Ceritinib Clinical Study - Cohort Actionable In a retrospective study, ALK G1202R was identified in 33% (23/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542). 31358542
ALK rearrange ALK G1202R lung non-small cell carcinoma predicted - resistant ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in progressive disease in a patient with ALK-rearranged non-small cell lung cancer refractory to Alecensa (alectinib) treatment, ALK G1202R was identified in post-brigatinib biopsy (PMID: 29935304). 29935304
ALK rearrange ALK G1202R lung non-small cell carcinoma predicted - resistant ALK Inhibitor Brigatinib Clinical Study - Cohort Actionable In a retrospective study, ALK G1202R was identified in 33% (23/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542). 31358542
ALK rearrange ALK G1202R lung non-small cell carcinoma predicted - resistant ALK Inhibitor Ensartinib Clinical Study - Cohort Actionable In a retrospective study, ALK G1202R was identified in 33% (23/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542). 31358542
ALK rearrange RB1 C706F TP53 loss lung small cell carcinoma predicted - resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, RB1 C706F and loss of exons 1-11 in TP53 were identified in the pericardium infiltrating small cell lung cancer that developed while on Lorlatinib (PF-06463922) treatment in a patient with ALK-rearranged non-small cell lung carcinoma (PMID: 28285684). 28285684
ALK rearrange ALK G1123S lung adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in rapid response in a patient with ALK-rearranged lung adenocarcinoma with an acquired ALK G1123S mutation, whose disease had relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233). 26134233
ALK rearrange ALK G1123S lung adenocarcinoma predicted - resistant ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, ALK G1123S was identified as an acquired mutation in a patient with ALK-rearranged lung adenocarcinoma whose disease relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233). 26134233
ALK rearrange ALK amp lung non-small cell carcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a retrospective analysis, two non-small cell lung cancer patients harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and were found to have acquired ALK amplification (PMID: 25724526). 25724526
ALK rearrange ALK amp lung non-small cell carcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical study, three patients with non-small cell lung carcinoma co-harboring an ALK rearrangement and ALK amplification demonstrated resistance to Xalkori (crizotinib) treatment (PMID: 27432227). 27432227
ALK rearrange ALK V1180L lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical study, Alunbrig (brigatinib) treatment resulted in 1 partial response and 1 stable disease in a total of 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK V1180L (PMID: 29935304). 29935304
ALK rearrange ALK V1180L lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Clinical Study - Cohort Actionable In a retrospective study, ALK V1180L was identified in 11% (5/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542). 31358542
ALK rearrange ALK V1180L lung non-small cell carcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical study, ALK V1180L was identified in post-progression biopsies of 2 non-small cell lung cancer patients harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304). 29935304
ALK rearrange TP53 mut lung non-small cell carcinoma decreased response ALK Inhibitor Crizotinib Clinical Study - Cohort Actionable In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Xalkori (crizotinib) as a first line therapy or after chemotherapy vs. patients with wild-type TP53 (5.0 mo., n=22 vs. 14.0 mo., n=71; p<0.001), and a lower median overall survival (17.0 mo., n=13 vs. not reached n=50; p=0.049) (PMID: 30165392). 30165392
ALK rearrange TP53 mut lung non-small cell carcinoma decreased response ALK Inhibitor Ceritinib Clinical Study - Cohort Actionable In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039), and a lower median overall survival with treatment with Zykadia (ceritinib) after Xalkori (crizotinib) of 7.0 mo. vs. 50.0 mo. in patients with wild-type TP53 (p=0.001) (PMID: 30165392). 30165392
ALK rearrange TP53 mut lung non-small cell carcinoma decreased response ALK Inhibitor Brigatinib Clinical Study - Cohort Actionable In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039) (PMID: 30165392). 30165392
ALK rearrange TP53 mut lung non-small cell carcinoma decreased response ALK Inhibitor Alectinib Clinical Study - Cohort Actionable In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039) (PMID: 30165392). 30165392
ALK rearrange ALK E1210K lung non-small cell carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer demonstrated disease progression when treated with Xalkori (crizotinib) due to a secondary acquired resistance mutation, ALK E1210K (PMID: 27432227). 27432227
ALK rearrange ALK F1174X lung non-small cell carcinoma predicted - sensitive ALK Inhibitor 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 F1174X (n=12), with an objective response rate of 42% (5/12; 95% CI 15.0-72.0), a median duration of response not reached (NR), and a median progression-free survival of 7.4 months (95% CI 2.8-NR) (PMID: 30892989; NCT01970865). 30892989
ALK rearrange ALK G1202del lung non-small cell carcinoma predicted - sensitive ALK Inhibitor 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 G1202R or ALK G1202del (n=28), with an objective response rate of 57% (16/28; 95% CI 37.0-76.0), a median duration of response of 7 months (95% CI 6.1-24.4), and a median progression-free survival of 8.2 months (95% CI 5.6-25.6) (PMID: 30892989; NCT01970865). 30892989
ALK rearrange ALK L1152R lung adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with ALK-rearranged lung adenocarcinoma, which also harbored RB1 deletion and TP53 G154V and R158C mutations, was found to have an acquired ALK L1152R mutation in a biopsy of a pleural nodule following progression on Xalkori (crizotinib) and Zykadia (ceritinib), and was subsequently treated with Alecensa (alectinib), resulting in a partial response in all disease areas (PMID: 27091190). 27091190
ALK rearrange ALK L1152R lung adenocarcinoma predicted - resistant ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, a patient with ALK-rearranged lung adenocarcinoma, which also harbored RB1 deletion and TP53 G154V and R158C mutations, demonstrated a partial response following treatment with Zykadia (ceritinib), however, progressed after 4 months and was found to have an acquired ALK L1152R mutation in a biopsy of a pleural nodule (PMID: 27091190). 27091190
ALK rearrange ALK F1174C lung non-small cell carcinoma predicted - resistant ALK Inhibitor Lorlatinib Clinical Study - Cohort Actionable In a retrospective study, ALK F1174C/L was identified in 14% (4/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). 31358542
ALK rearrange ALK F1174L lung non-small cell carcinoma predicted - resistant ALK Inhibitor Lorlatinib Clinical Study - Cohort Actionable In a retrospective study, ALK F1174C/L was identified in 14% (4/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). 31358542
ALK rearrange ALK F1174L lung adenocarcinoma predicted - resistant ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, ALK F1174L was identified in biopsies at disease progression after 4 months of Zykadia (ceritinib) treatment in a patient with lung adenocarcinoma harboring ALK rearrangement (PMID: 31585938). 31585938
ALK rearrange ALK F1174L ALK G1202R lung non-small cell carcinoma predicted - resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588). 31439588
ALK rearrange ALK F1174C ALK G1202R lung non-small cell carcinoma predicted - resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588). 31439588
ALK rearrange ALK T1151M ALK G1202R lung non-small cell carcinoma predicted - resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588). 31439588
ALK rearrange ALK mut lung non-small cell carcinoma sensitive ALK Inhibitor Ceritinib Clinical Study - Cohort Actionable In a retrospective analysis, patients with ALK-rearrangement positive non-small cell lung cancer who acquired ALK drug resistance mutations following Xalkori (crizotinib) treatment had a median progression-free survival (mPFS) of 5.4 months on Zykadia (ceritinib), which was not significantly different than the mPFS of 6.5 months for patients without ALK mutations (PMID: 25724526). 25724526
ALK rearrange ROS1 rearrange lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a near complete response and progression-free survival for at least 55 months in a patient with non-small cell lung cancer harboring rearrangements in ALK and ROS1 (PMID: 34459458). 34459458
ALK rearrange ROS1 rearrange lung adenocarcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in lymph node response and progression-free survival greater than 1 year in a patient with EGFR wild-type lung adenocarcinoma harboring rearrangements in ALK and ROS1 (PMID: 29268402). 29268402
ALK rearrange ROS1 rearrange lung adenocarcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in decreased tumor size at 3 months in a patient with lung adenocarcinoma harboring rearrangements in ROS1 and ALK (PMID: 30327151). 30327151
ALK rearrange ROS1 rearrange lung adenocarcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in decreased tumor size and metabolism in a patient with lung adenocarcinoma harboring rearrangements in ROS1 and ALK (PMID: 28532565). 28532565
ALK R1192P Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK R1192P was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK R1192P malignant pheochromocytoma predicted - sensitive ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response (PR) after 2 months of therapy and a sustained PR at 10 months in a patient with malignant pheochromocytoma harboring ALK R1192P (PMID: 34371380). 34371380
ALK R1192P malignant pheochromocytoma no benefit ALK Inhibitor Alectinib + Octreotide Case Reports/Case Series Actionable In a clinical case study, addition of Alecensa (alectinib) to Octreotide treatment did not lead to a response in a patient with malignant pheochromocytoma harboring ALK R1192P, with a radiological stable disease after 1 month of treatment and disease progression after 5 months of treatment (PMID: 34371380). 34371380
EML4 - ALK ALK R1192P Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells overexpressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4 - ALK ALK R1192P Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4 - ALK ALK R1192P Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4 - ALK ALK R1192P Advanced Solid Tumor sensitive ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4 - ALK ALK R1192P Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK R1192P were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK R1192P Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK R1192P were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
ALK R1209Q colon cancer predicted - sensitive ALK Inhibitor Crizotinib + Pazopanib Case Reports/Case Series Actionable In a Phase I trial, Xalkori (crizotinib) and Votrient (pazopanib) combination treatment resulted in a partial response in a patient with colon cancer harboring ALK R1209Q (PMID: 33994796; NCT01548144). 33994796
ALK S1206R Advanced Solid Tumor predicted - sensitive ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK S1206R in an in vitro assay (PMID: 34158340). 34158340
EML4 - ALK ALK S1206R Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing ALK S1206R in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture and in cell line xenograft models (PMID: 22034911). 22034911
ALK negative leukemia resistant ALK Inhibitor CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 did not inhibit growth of ALK-negative leukemia cells in culture (PMID: 22203728). 22203728
ALK negative lymphoma resistant ALK Inhibitor CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 did not inhibit growth of ALK-negative lymphoma cells in culture (PMID: 22203728). 22203728
ALK negative lung non-small cell carcinoma resistant ALK Inhibitor CEP-28122 Preclinical - Cell line xenograft Actionable In a preclinical study, ALK negative non-small cell lung carcinoma cells were resistant to CEP-28122 in culture and in cell line xenograft models (PMID: 22203728). 22203728
ALK negative colon carcinoma resistant ALK Inhibitor CEP-28122 Preclinical - Cell line xenograft Actionable In a preclinical study, CEP-28122 did not inhibit tumor growth in cell line xenograft models of ALK-negative colon carcinoma (PMID: 22203728). 22203728
ALK negative anaplastic large cell lymphoma predicted - sensitive Brentuximab vedotin Phase II Actionable In a Phase II trial (SGN-35), Adcetris (brentuximab vedotin) treatment resulted in complete remission in 57% (33/58), partial remission in 29% (17/58) of patients with relapsed or refractory systemic anaplastic large cell lymphoma, 72% (42/58) of the patients were ALK-negative (PMID: 22614995; NCT00866047). 22614995
ROS1 rearrange ALK neg lung non-small cell carcinoma sensitive ALK Inhibitor Crizotinib Phase II Actionable In a Phase II trial, Xalkori (crizotinib) treatment resulted in an objective response rate of 69% (89/129), and a median duration of treatment of 7.8 months in ALK negative, ROS1 rearranged non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9022); NCT01945021). detail...
EML4 - ALK ALK A1200_G1201delinsW lung adenocarcinoma predicted - sensitive ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK who developed resistance to Alecensa (alectinib) following acquisition of ALK A1200_G1201delinsW demonstrated symptom improvement and stable disease for 4 months with Alunbrig (brigatinib) treatment (PMID: 34548910). 34548910
EML4 - ALK ALK A1200_G1201delinsW lung adenocarcinoma predicted - resistant ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, post treatment biopsy analysis of a lung adenocarcinoma patient initially harboring EML4-ALK who developed progressive disease after 20 months of Alecensa (alectinib) treatment revealed acquisition of ALK A1200_G1201delinsW (PMID: 34548910). 34548910
ALK E1210K Advanced Solid Tumor predicted - sensitive ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK E1210K in an in vitro assay (PMID: 34158340). 34158340
EML4 - ALK ALK E1210K Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK E1210K Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK E1210K Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK E1210K Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK E1210K lung non-small cell carcinoma resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical study, a patient with non-small cell lung carcinoma harboring EML4-ALK progressed on treatment with Xalkori (crizotinib) and was subsequently found to harbor a secondary resistance mutation, ALK E1210K (PMID: 29636358). 29636358
ALK G1269S Advanced Solid Tumor decreased response ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, ALK G1269S demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340). 34158340
EML4 - ALK ALK G1269S Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing ALK G1269S in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture and in cell line xenograft models (PMID: 22034911). 22034911
EML4 - ALK ALK G1269S Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269S in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 21948233). 21948233
EML4 - ALK ALK G1269S Advanced Solid Tumor resistant ALK Inhibitor TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269S in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK L1256F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1256F 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 L1256F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F lung adenocarcinoma resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) did not inhibit Alk kinase activity or proliferation of lung adenocarcinoma cells expressing ALK L1256F in the context of EML4-ALK in cell culture (PMID: 30662002). 30662002
EML4 - ALK ALK L1256F Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F lung adenocarcinoma sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited Alk kinase activity and proliferation of lung adenocarcinoma cells expressing ALK L1256F in the context of EML4-ALK in cell culture (PMID: 30662002). 30662002
EML4 - ALK ALK L1256F Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F 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 L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK E1303K lung non-small cell carcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical study, a patient with non-small cell lung cancer harboring EML4-ALK and ALK E1303K developed progressive disease 7 days after Xalkori (crizotinib) treatment (PMID: 29978950). 29978950
ALK R1275L neuroblastoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a Phase I/II trial, Xalkori (crizotinib) treatment was well-tolerated and resulted in stable disease in a pediatric patient with neuroblastoma harboring ALK R1275L who stayed on treatment for 4 cycles (PMID: 23598171; NCT00939770). 23598171
ALK F1174L neuroblastoma predicted - sensitive ALK Inhibitor Entrectinib Case Reports/Case Series Actionable In a Phase I/II trial, Rozlytrek (entrectinib) treatment resulted in a complete response in a patient with neuroblastoma harboring ALK F1174L (PMID: 35395680; NCT02650401). 35395680
ALK F1174L neuroblastoma sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK F1174L (corresponds to F1178L in mouse) and subsequent upregulation of Ret (PMID: 24811913). 24811913
ALK F1174L Advanced Solid Tumor predicted - sensitive ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1174L in an in vitro assay (PMID: 34158340). 34158340
ALK F1174L neuroblastoma conflicting ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, neuroblastoma cells harboring ALK F1174L were resistant to Lorbrena (lorlatinib) in culture (PMID: 30322862). 30322862
ALK F1174L neuroblastoma conflicting ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response lasting 13 mo in a pediatric patient with metastatic, relapsed neuroblastoma harboring ALK F1147L and PIK3CA C692Ffs*8, who had previously progressed on combination therapy with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan (PMID: 34210658). 34210658
ALK F1174L neuroblastoma conflicting ALK Inhibitor Lorlatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells over expressing ALK F1174L in culture, and induced rapid and sustained complete tumor regression in both patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). 26554404
ALK F1174L neuroblastoma sensitive ALK Inhibitor AZD3463 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD3463 inhibited growth of neuroblastoma cells harboring ALK F1174L in culture, resulted in near complete tumor regression in cell line xenograft models (PMID: 26786851). 26786851
ALK F1174L neuroblastoma no benefit ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Case Reports/Case Series Actionable In a clinical case study, combination treatment with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan resulted in progressive disease within 1 cycle of therapy in a pediatric patient with metastatic, relapsed neuroblastoma harboring ALK F1147L and PIK3CA C692Ffs*8 (PMID: 34210658). 34210658
ALK F1174L neuroblastoma no benefit ALK Inhibitor Crizotinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1174L in culture, and only delayed tumor growth in patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). 26554404
ALK F1174L neuroblastoma no benefit ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, although all 3 patients harboring ALK F1174L had disease progression after only 1 cycle of treatment (PMID: 33568345; NCT00939770). 33568345
ALK F1174L neuroblastoma sensitive ALK Inhibitor CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 inhibited growth of neuroblastoma cells harboring ALK F1174L in culture (PMID: 22203728). 22203728
ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK F1174L was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK F1174L in culture (PMID: 26554404). 26554404
ALK F1174L TP53 wild-type neuroblastoma sensitive ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in xenograft models of a crizotinib-resistant human neuroblastoma cell line harboring ALK F1174L and wild-type TP53 (PMID: 26438783). 26438783
EML4 - ALK ALK F1174L Advanced Solid Tumor conflicting ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK F1174L in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) in culture (PMID: 27780853). 27780853
EML4 - ALK ALK F1174L Advanced Solid Tumor conflicting ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859). 27009859
EML4 - ALK ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174L in culture and in xenograft models (PMID: 24887559). 24887559
EML4 - ALK ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859). 27009859
EML4 - ALK ALK F1174L Advanced Solid Tumor predicted - resistant ALK Inhibitor XMU-MP-5 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L did not demonstrate sensitivity to treatment with XMU-MP-5 in culture (PMID: 34845836). 34845836
EML4 - ALK ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 35421578). 35421578
EML4 - ALK ALK F1174L Advanced Solid Tumor resistant ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK F1174L Advanced Solid Tumor conflicting ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were less sensitive to Alunbrig (brigatinib)-mediated growth inhibition compared to cells expressing EML4-ALK in culture (PMID: 27009859). 27009859
EML4 - ALK ALK F1174L Advanced Solid Tumor conflicting ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 35421578). 35421578
EML4 - ALK ALK F1174L Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were resistant to Zykadia (ceritinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859). 27009859
EML4 - ALK ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK F1174L in the context of EML4-ALK in culture (PMID: 26144315). 26144315
ALK F1174L ALK L1198P neuroblastoma resistant ALK Inhibitor TAE684 Preclinical - Cell culture Actionable In a preclinical study, expression of ALK L1198P in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233). 21948233
ALK F1174L ALK L1198P neuroblastoma resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, expression of ALK L1198P in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to Xalkori (crizotinib) in culture (PMID: 21948233). 21948233
ALK G1123S ALK F1174L neuroblastoma resistant ALK Inhibitor TAE684 Preclinical - Cell culture Actionable In a preclinical study, expression of ALK G1123S in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233). 21948233
ALK G1123D ALK F1174L neuroblastoma resistant ALK Inhibitor TAE684 Preclinical - Cell culture Actionable In a preclinical study, expression of ALK G1123D in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233). 21948233
ALK F1174L ALK amp neuroblastoma sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174L in culture (PMID: 29907598). 29907598
ALK F1174L ALK amp neuroblastoma sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174L in culture (PMID: 29907598). 29907598
ALK F1174L ALK pos lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Ensartinib Case Reports/Case Series Actionable In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 71% (5/7, all partial responses) of patients with ALK-positive non-small cell lung cancer harboring ALK F1174L (n=5) or ALK F1174V (n=1) (PMID: 31628085; NCT0321569). 31628085
EML4 - ALK ALK F1174L ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK F1174L and ALK G1202R compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938). 31585938
ALK Y1278S Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK Y1278S was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
EML4 - ALK ALK C1156Y ALK F1174I Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174I 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 F1174I Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I 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 F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor resistant ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174I were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor predicted - resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174I demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK E1154K ALK G1202R ALK I1268V lung adenocarcinoma predicted - resistant ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, Zykadia (ceritinib) treatment resulted rapid disease progression in a patient with lung adenocarcinoma harboring EML4-ALK, with acquired ALK G1202R and ALK E1154K in tumor biopsies, and ALK G1202R and ALK I1268V in ctDNA (PMID: 31585938). 31585938
EML4 - ALK ALK E1154K ALK G1202R ALK I1268V lung adenocarcinoma predicted - resistant ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response lasting 9.2 months in a patient with lung adenocarcinoma harboring EML4-ALK, at disease progression, ALK G1202R and ALK E1154K were identified in biopsies, while ALK G1202R and ALK I1268V were identified in ctDNA (PMID: 31585938). 31585938
EML4 - ALK ALK G1202K lung adenocarcinoma predicted - sensitive ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, fourth-line Lorbrena (lorlatinib) treatment resulted in symptom improvement and response in lung disease with a progression-free survival lasting 4 months in an EML4-ALK positive a patient with lung adenocarcinoma patient harboring EML4-ALK and an acquired ALK G1202K, who had previously progressed on Xalkori (crizotinib) and Alecensa (alectinib) treatment (PMID: 33790576). 33790576
ALK L1152P Advanced Solid Tumor decreased response ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, ALK L1152P demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340). 34158340
EML4 - ALK ALK L1152P Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1152P in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK L1152P Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152P in culture (PMID: 35421578). 35421578
EML4 - ALK ALK L1152P Advanced Solid Tumor sensitive ALK Inhibitor WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152P in culture (PMID: 35421578). 35421578
EML4 - ALK ALK L1152P Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152P demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 24675041). 24675041
EML4 - ALK ALK L1152P Advanced Solid Tumor resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152P in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK L1152P Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152P in the context of EML4-ALK demonstrated reduced sensitivity to Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK S1206F lung adenocarcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in clinical improvement within one week of therapy, a 30.3% decrease in target lesion and a partial response after 2 months, and an ongoing response after 4 months in a patient with lung adenocarcinoma harboring de novo EML4-ALK-(E5;A20) and ALK S1206F (PMID: 27565908). 27565908
EML4 - ALK ALK S1206F Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK S1206F in the context of EML4-ALK in culture (PMID: 27780853). 27780853
ALK amp neuroblastoma sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of ALK amplified neuroblastoma cells in culture (PMID: 26554404). 26554404
ALK amp lung non-small cell carcinoma no benefit ALK Inhibitor Belizatinib Phase I Actionable In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488). 31217479
ALK amp neuroblastoma sensitive ALK Inhibitor CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 inhibited growth of ALK-amplified neuroblastoma cells in culture (PMID: 22203728). 22203728
ALK amp neuroblastoma no benefit ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) was less efficient than Lorlatinib (PF-06463922) to induced growth inhibition in ALK-amplified neuroblastoma cells in culture (PMID: 26554404). 26554404
ALK amp neuroblastoma no benefit ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, although both patients harboring ALK amplification had disease progression after only 1 cycle of treatment (PMID: 33568345; NCT00939770). 33568345
ALK amp TP53 wild-type neuroblastoma sensitive ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in neuroblastoma cell lines harboring Alk amplification and functional TP53, resulting in growth inhibition in culture (PMID: 26438783). 26438783
ALK F1174V ALK amp neuroblastoma sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174V in culture (PMID: 29907598). 29907598
ALK F1174V ALK amp neuroblastoma sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174V in culture (PMID: 29907598). 29907598
ALK amp ALK pos lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Ensartinib Case Reports/Case Series Actionable In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 56% (5/9, all partial responses) and stable disease in 44% (4/9) of patients with ALK-positive non-small cell lung cancer with ALK amplification (PMID: 31628085; NCT0321569). 31628085
ALK L1198F Advanced Solid Tumor predicted - sensitive ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK L1198F in an in vitro assay (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK L1198F lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK positive non-small lung cancer initially responded to Xalkori (crizotinib) but developed resistance with the emergence of a secondary ALK mutation C1156Y, and subsequently redeveloped sensitivity to Xalkori (crizotinib) upon the emergence of a second ALK mutation, L1198F arising from resistance to Lorlatinib (PF-06463922) (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK C1156Y and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and ALK L1198F in the context of EML4-ALK were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK L1198F lung non-small cell carcinoma resistant ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, a patient with EML4-ALK positive non-small lung cancer with a secondary Xalkori (critzotinib) resistance mutation C1156Y, responded to Lorlatinib (PF-06463922) but subsequently developed resistance upon the emergence of a second ALK mutation, L1198F (PMID: 26698910; NCT01970865). 26698910
EML4 - ALK ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with L1198F in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F Advanced Solid Tumor predicted - sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F Advanced Solid Tumor predicted - sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F had reduced sensitivity to growth inhibition mediated by Lorbrena (lorlatinib) in comparison to wild-type EML4-ALK in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing L1198F in the context of EML4-ALK in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F Advanced Solid Tumor conflicting ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F Advanced Solid Tumor conflicting ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F demonstrated sensitivity to Alecensa (alectinib) treatment in culture (PMID: 27432227). 27432227
EML4 - ALK ALK L1198F Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F Advanced Solid Tumor conflicting ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F 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 L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK F1174C ALK L1198F Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). 26698910
EML4 - ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant ALK Inhibitor Brigatinib