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Gene ALK
Variant L1198F
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions ALK L1198F lies within the protein kinase domain of the Alk protein (UniProt.org). L1198F confers a gain of function to the Alk protein as demonstrated by increased Alk kinase activity and downstream Pi3k and Mapk pathway activation (PMID: 21596819).
Associated Drug Resistance
Category Variants Paths

ALK mutant ALK act mut ALK L1198F

ALK mutant ALK L1198X ALK L1198F

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Transcript NM_004304.5
gDNA chr2:g.29220759G>A
cDNA c.3592C>T
Protein p.L1198F
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004304.4 chr2:g.29220759G>A c.3592C>T p.L1198F RefSeq GRCh38/hg38
NM_004304 chr2:g.29220759G>A c.3592C>T p.L1198F RefSeq GRCh38/hg38
NM_004304.5 chr2:g.29220759G>A c.3592C>T p.L1198F RefSeq GRCh38/hg38

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  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK rearrange ALK C1156Y ALK L1198F 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 C1156Y ALK L1198F developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
EML4 - ALK ALK C1156Y ALK L1198F lung non-small cell carcinoma resistant 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 C1156Y ALK L1198F lung non-small cell carcinoma predicted - sensitive 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 sensitive 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 sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 35726063). 35726063
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant 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 resistant 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 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 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 Advanced Solid Tumor resistant 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 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 Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to Zykadia (ceritinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 35726063). 35726063
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor conflicting 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 conflicting 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 sensitive 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 L1198F Advanced Solid Tumor sensitive 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 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 predicted - sensitive 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 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 conflicting 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 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 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 conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, a cell line expressing EML4-ALK with ALK L1198F was resistant to Zykadia (ceritinib) in culture (PMID: 31446141). 31446141
EML4 - ALK ALK L1198F Advanced Solid Tumor conflicting 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 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 sensitive 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 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 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 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 L1198F Advanced Solid Tumor sensitive 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 sensitive Ensartinib Preclinical - Cell culture Actionable In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK L1198F in culture (PMID: 31446141). 31446141
EML4 - ALK ALK F1174C ALK L1198F Advanced Solid Tumor sensitive 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 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 resistant 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 F1174C ALK L1198F Advanced Solid Tumor resistant 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 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 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 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 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 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 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 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 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 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 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 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 L1198F ALK G1202R Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK 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 L1198F ALK G1202R Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F and G1202R in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F 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 L1198F compound mutation in the context of EML4-ALK culture and resulted in only 30% tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F 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 L1198F displayed enhanced resistance to growth inhibition mediated by Lorbrena (lorlatinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R 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 L1198F 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 L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK 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 Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant 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 Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and L1198F 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 Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F 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 L1198F 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 L1198F ALK G1202R Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F ALK G1202R 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 and G1202R in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were re-sensitized and became modestly sensitive to Xalkori (crizotinib) with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A and L1198F in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
ALK rearrange ALK I1171N ALK L1198F lung non-small cell carcinoma resistant 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
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F, ALK G1202R, and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, G1269A, and L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A, L1198F, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor conflicting 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 conflicting 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 Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 35726063). 35726063
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant 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 Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F were resistant to Alecensa (alectinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant 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 resistant 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 L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F were resistant to Zykadia (ceritinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant 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 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 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 predicted - resistant 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 resistant 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 Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant 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 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 sensitive 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
ALK C1156Y ALK L1198F Advanced Solid Tumor predicted - sensitive TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK C1156Y and ALK L1198F compound mutation in an in vitro assay (PMID: 34158340). 34158340
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
ALK L1198F ALK G1202R Advanced Solid Tumor predicted - sensitive TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK G1202R and L1198F compound mutation in an in vitro assay (PMID: 34158340). 34158340
ALK fusion ALK C1156Y ALK L1198F lung non-small cell carcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK L1198F was identified as an acquired mutation in a non-small cell lung cancer patient harboring an ALK fusion with ALK C1156Y who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). 35726063
EML4 - ALK ALK C1156Y ALK I1171T ALK L1198F lung non-small cell carcinoma resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK (e6:e19) with ALK C1156Y, I1171T, and L1198F was resistant to Lorbrena (lorlatinib) in culture (PMID: 37748191). 37748191
EML4 - ALK ALK C1156Y ALK I1171T ALK L1198F lung non-small cell carcinoma sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited viability of a patient-derived non-small cell lung cancer cell line harboring EML4-ALK (e6:e19) with ALK C1156Y, I1171T, and L1198F in culture (PMID: 37748191). 37748191
EML4 - ALK ALK C1156Y ALK I1171T ALK L1198F lung non-small cell carcinoma sensitive Afatinib + Crizotinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Gilotrif (afatinib) and Xalkori (crizotinib) further inhibited viability of a patient-derived non-small cell lung cancer cell line harboring EML4-ALK (e6:e19) with ALK C1156Y, I1171T, and L1198F compared to Xalkori (crizotinib) alone in culture (PMID: 37748191). 37748191