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Gene ALK
Variant L1196M
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions ALK L1196M lies within the protein kinase domain of the Alk protein (UniProt.org). L1196M results in increased Alk kinase activity (PMID: 30258533), modest Alk autophosphorylation, and transformation in cell culture (PMID: 25517749), and confers resistance to Alk inhibitors in the context of ALK rearrangements in culture and in vivo (PMID: 21613408, PMID: 25421750, PMID: 31452835).
Associated Drug Resistance Y

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Transcript NM_004304.4
gDNA chr2:g.29220765G>T
cDNA c.3586C>A
Protein p.L1196M
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004304.4 chr2:g.29220765G>T c.3586C>A p.L1196M RefSeq GRCh38/hg38
NM_004304 chr2:g.29220765G>T c.3586C>A p.L1196M RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK L1196M neuroblastoma predicted - sensitive 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
ALK L1196M Advanced Solid Tumor sensitive 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 Advanced Solid Tumor predicted - sensitive 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
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive 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 Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 26698910) 26698910
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1196M lung non-small cell carcinoma sensitive 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 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 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 conflicting 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 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 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 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 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 sensitive 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 Advanced Solid Tumor conflicting 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 conflicting 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 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 sensitive XMU-MP-5 Preclinical - Cell line xenograft Actionable In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34845836). 34845836
EML4 - ALK ALK L1196M lung adenocarcinoma predicted - resistant 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 Advanced Solid Tumor sensitive 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 sensitive 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 resistant 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 resistant 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 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 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 sensitive 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 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 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 Advanced Solid Tumor sensitive 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 lung non-small cell carcinoma sensitive 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 resistant 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 lung non-small cell carcinoma sensitive 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 ALK L1198F Advanced Solid Tumor resistant 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 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 L1198F Advanced Solid Tumor resistant 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 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 sensitive 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 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 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 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 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 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 resistant 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 G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK L1196M ALK G1269A lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a patient with non-small cell lung cancer harboring EML4-ALK demonstrated a partial response when treated with Xalkori (crizotinib), however, after 6 months the patient progressed and was found to harbor two secondary resistance mutations, ALK G1269A and ALK L1196M (PMID: 23344087). 23344087
EML4 - ALK ALK C1156Y ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK C1156Y 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 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
ALK rearrange ALK L1196M lung non-small cell carcinoma predicted - resistant 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 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 adenocarcinoma predicted - resistant 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 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 non-small cell carcinoma predicted - resistant 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 resistant 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 resistant 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 predicted - sensitive Lorlatinib Clinical Study Actionable In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK 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 I1171S ALK L1196M Advanced Solid Tumor resistant 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
EML4 - ALK ALK F1174C ALK L1196M Advanced Solid Tumor resistant 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 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 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 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 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 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 Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1196M were resistant to Xalkori (crizotinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant 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 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 Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and L1196M compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorbrena (lorlatinib) treatment did not inhibit proliferation of transformed cells expressing ALK G1202R and L1196M compound mutation in the context of EML4-ALK in culture and resulted in only 18% tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant 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 Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1196M were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell line xenograft Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1196M and ALK G1202R compound mutation in the context of EML4-ALK in culture, and resulted in complete tumor growth regression in a cell line xenograft model (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1196M were resistant to Alecensa (alectinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant 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 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 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 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 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 sensitive 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 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 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 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 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 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 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 resistant 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 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 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 predicted - resistant 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 resistant 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 L1196M ALK D1203N Advanced Solid Tumor resistant 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 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 I1171N ALK L1196M Advanced Solid Tumor resistant 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 I1171N ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and 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 malignant pleural mesothelioma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK L1196M and ALK I1171N were identified in the post-progression biopsy of a patient with malignant pleural mesothelioma harboring EML4-ALK who previously responded to Alecensa (alectinib) treatment (PMID: 32600123). 32600123
EML4 - ALK ALK I1171N ALK L1196M malignant pleural mesothelioma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in tumor regression and a partial response lasting 3.6 months in a patient with malignant pleural mesothelioma harboring EML4-ALK, ALK L1196M, and ALK I1171N (PMID: 32600123). 32600123
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor resistant 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 sensitive 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 resistant 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 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 C1156Y ALK L1196M ALK G1202R lung non-small cell carcinoma predicted - resistant 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 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 I1171N ALK L1196M ALK G1202R malignant pleural mesothelioma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R was identified in the post-progression biopsy of a patient with malignant pleural mesothelioma harboring EML4-ALK with ALK L1196M and ALK I1171N who previously responded to Lorbrena (lorlatinib) treatment (PMID: 32600123). 32600123
ALK fusion ALK L1196M ALK G1202R lung non-small cell carcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK L1196M was identified as an acquired mutation in a non-small cell lung cancer patient harboring an ALK fusion with ALK G1202R who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). 35726063
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK mutant lung non-small cell carcinoma no benefit 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 mutant lung non-small cell carcinoma no benefit 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...