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| Gene | ALK |
| Variant | G1202R |
| Impact List | missense |
| Protein Effect | unknown |
| Gene Variant Descriptions | ALK G1202R lies within the protein kinase domain of the Alk protein (UniProt.org). G1202R demonstrates increased colony formation, decreased Cdh1 expression, increased migration and invasion, increased expression of metastatic factors Cdh2, Vim, Mmp2, Mmp9, and Slug in cell culture in the context of EML4-ALK (PMID: 35085771), and drug resistance in the context of ALK fusions (PMID: 22277784, PMID: 24736079, PMID: 35085771), but has not been individually characterized and therefore, its effect on Alk protein function is unknown. |
| Associated Drug Resistance | Y |
| Category Variants Paths |
ALK mutant ALK G1202X ALK G1202R |
| Transcript | NM_004304.5 |
| gDNA | chr2:g.29220747C>T |
| cDNA | c.3604G>A |
| Protein | p.G1202R |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_004304.4 | chr2:g.29220747C>T | c.3604G>A | p.G1202R | RefSeq | GRCh38/hg38 |
| NM_004304.5 | chr2:g.29220747C>T | c.3604G>A | p.G1202R | RefSeq | GRCh38/hg38 |
| NM_004304 | chr2:g.29220747C>T | c.3604G>A | p.G1202R | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| EML4 - ALK ALK G1202R | lung non-small cell carcinoma | resistant | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who acquired the secondary drug resistance mutation, ALK S1206Y, when treated with Xalkori (crizotinib) was subsequently treated with Zykadia (ceritinib), developed drug resistance, and was then found to have lost the ALK S1206Y mutation, but gained ALK G1202R (PMID: 24675041). | 24675041 |
| EML4 - ALK ALK G1202R | lung non-small cell carcinoma | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were insensitive to Zykadia (ceritinib) in culture (PMID: 24675041). | 24675041 |
| EML4 - ALK ALK G1202R | lung cancer | conflicting | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis in transformed cells over expressing ALK G1202R in the context of EML4-ALK in culture and in cell line xenograft models (PMID: 26144315). | 26144315 |
| EML4 - ALK ALK G1202R | lung cancer | conflicting | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). | 26698910 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to Rozlytrek (entrectinib) in culture (PMID: 26939704). | 26939704 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). | 22277784 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). | 25727400 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910). | 26698910 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Alecensa (alectinib) did not effectively inhibit growth of transformed cells expressing EML4-ALK with ALK G1202R in culture, and did not inhibit tumor growth in xenograft models (PMID: 24887559). | 24887559 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Alecensa (alectinib) in culture (PMID: 25727400). | 25727400 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). | 26698910 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Zykadia (ceritinib) in culture (PMID: 25727400). | 25727400 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). | 26698910 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853). | 27780853 |
| EML4 - ALK ALK G1202R | 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 G1202R in culture (PMID: 35421578). | 35421578 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Alunbrig (brigatinib) in culture (PMID: 25727400). | 25727400 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited tumor growth of a cell line xenograft model expressing EML4-ALK with ALK G1202R (PMID: 35820889). | 35820889 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment inhibited tumor growth in a mouse cell line xenograft model expressing EML4-ALK and ALK G1202R (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202R demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). | 27432227 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | sensitive | Repotrectinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Augtyro (repotrectinib) inhibited Alk activity and proliferation of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 30093503). | 30093503 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | sensitive | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Augtyro (repotrectinib) inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK G1202R in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK, who had developed resistance to Xalkori (crizotinib), was found to harbor ALK G1202R following treatment with Alecensa (alectinib) (PMID: 24736079). | 24736079 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | ASP3026 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to ASP3026 in culture (PMID: 25727400). | 25727400 |
| EML4 - ALK ALK G1202R | lung adenocarcinoma | conflicting | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK, with acquired ALK G1202R and ALK E1154K in tumor biopsies, and ALK G1202R and ALK I1268V in ctDNA, experienced disease progression after 2.5 months of Alunbrig (brigatinib) treatment, and only increased allelic frequency of ALK G1202R was detected at disease progression (PMID: 31585938). | 31585938 |
| EML4 - ALK ALK G1202R | lung adenocarcinoma | conflicting | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response and 30 months of progression-free survival in a lung adenocarcinoma patient harboring EML4-ALK and de novo ALK G1202R (PMID: 35235872). | 35235872 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | sensitive | TPX-0131 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TPX-0131 inhibited Alk autophosphorylation and proliferation of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture and resulted in complete tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | sensitive | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, TPX-0131 treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK G1202R in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to Xospata (gilteritinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | predicted - sensitive | NUV-655 | Preclinical - Cell culture | Actionable | In a preclinical study, NUV-655 treatment resulted in decreased cell growth in a cell line expressing EML4-ALK fusion and ALK G1202R in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1468). | detail... |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | sensitive | XMU-MP-5 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1202R in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34845836). | 34845836 |
| EML4 - ALK ALK G1202R | lung non-small cell carcinoma | sensitive | Ceritinib + HJC0152 | Preclinical - Cell culture | Actionable | In a preclinical study, HJC0152 and Zykadia (ceritinib) combination treatment increased apoptosis and decreased viability and colony formation in a non-small cell lung cancer cell line expressing EML4-ALK and ALK G1202R compared to either drug alone in culture (PMID: 35085771). | 35085771 |
| EML4 - ALK ALK G1202R | lung non-small cell carcinoma | sensitive | HJC0152 | Preclinical - Cell culture | Actionable | In a preclinical study, HJC0152 treatment decreased Stat signaling, migration, and invasion in a non-small cell lung cancer cell line expressing EML4-ALK and ALK G1202R in culture (PMID: 35085771). | 35085771 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | sensitive | Iruplinalkib | Preclinical - Cell culture | Actionable | In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1202R in culture (PMID: 35421578). | 35421578 |
| EML4 - ALK ALK G1202R | lung squamous cell carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK G1202R was identified in the post-progression biopsy of a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK, who previously responded to Alunbrig (brigatinib) treatment (PMID: 34376997). | 34376997 |
| EML4 - ALK ALK G1202R | lung squamous cell carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, third-line Lorbrena (lorlatinib) treatment resulted in a progression-free survival of 7 months in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK and ALK G1202R (PMID: 34376997). | 34376997 |
| EML4 - ALK ALK G1202R | lung adenocarcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK G1202R was identified in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) after the disease progressed on Alecensa (alectinib) treatment (PMID: 35328235). | 35328235 |
| EML4 - ALK ALK G1202R | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with lung adenocarcinoma harboring EML4-ALK (e6a:e20) and ALK G1202R (PMID: 35328235). | 35328235 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | sensitive | APG-2449 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, APG-2449 inhibited tumor growth of a cell line xenograft model expressing EML4-ALK with ALK G1202R (PMID: 35820889). | 35820889 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, a cell line expressing EML4-ALK with ALK G1202R was resistant to Ensartinib (X-396) in culture (PMID: 31446141). | 31446141 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to Ensartinib (X-396) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK G1202R | lung non-small cell carcinoma | predicted - sensitive | NUV-655 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, NUV-655 demonstrated activity in a patient-derived non-small cell lung cancer cell line harboring EML4-ALK with ALK G1202R in culture and induced tumor regression in a patient-derived xenograft (PDX) model (Eur J Cancer 2022 Vol 174, Supp 1:S78-S79). | detail... |
| EML4 - ALK ALK G1202R | lung non-small cell carcinoma | predicted - sensitive | Lorlatinib + PF-07284892 | Case Reports/Case Series | Actionable | In a clinical case study, the combination of PF-07284892 and Lorbrena (lorlatinib) resulted in a partial response with a 50% tumor reduction after 6 weeks in a patient with non-small cell lung cancer harboring EML4-ALK and ALK G1202R, and the patient remained on the combination for 4.5 months (PMID: 37269335; NCT04800822). | 37269335 |
| ALK fusion ALK G1202R | lung non-small cell carcinoma | sensitive | 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... |
| 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 |
| ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | 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 | 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 | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK G1202R was identified in 13% (7/52) of patients with non-small cell lung cancer harboring an ALK rearrangement after disease progression on first-line Alecensa (alectinib), and in 32% (18/56) patients who responded to second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
| ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | 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 | 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 | 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 | 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 | 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 ALK G1202R | lung non-small cell carcinoma | 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 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 | Lorlatinib | Guideline | Actionable | Lorbrena (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 - sensitive | Ficonalkib | Case Reports/Case Series | Actionable | In a Phase I/II trial, Ficonalkib (SY-3505) treatment was well tolerated and resulted in an objective response rate (ORR) of 47.5% (38/80, all partial responses (PR)), a disease control rate of 92.5%, median duration of response of 9.23 months, and median progression-free survival of 7.95 in Chinese patients with ALK-positive non-small cell lung cancer, with an ORR of 70% (7/10) in patients with ALK G1202R (PMID: 38295954; NCT05257512). | 38295954 |
| EML4 - ALK ALK F1174V ALK G1202R | lung non-small cell carcinoma | sensitive | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who was previously treated with Xalkori (crizotinib) and subsequently developed the resistance mutation, ALK G1269A, was treated with Zykadia (ceritinib), later progressed, and was found to have lost ALK G1269A, but gained ALK F1174V and ALK G1202R (PMID: 24675041). | 24675041 |
| 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, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512). | 38448512 |
| 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, 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 G1202R and L1196M were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
| 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 | 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 | sensitive | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, TPX-0131 treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK G1202R and L1196M in culture (PMID: 36201110). | 36201110 |
| 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 | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and L1196M were resistant to Xospata (gilteritinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK L1196M ALK G1202R | Advanced Solid Tumor | 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 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 | 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 | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Alecensa (alectinib) in culture (PMID: 38448512). | 38448512 |
| 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 | 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 G1202R and L1196M were resistant to Alecensa (alectinib) in culture (PMID: 36201110). | 36201110 |
| 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 | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Xalcori (crizotinib) in culture (PMID: 38448512). | 38448512 |
| 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 | 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 EML4-ALK with ALK G1202R and L1196M were resistant to Xalkori (crizotinib) in culture (PMID: 36201110). | 36201110 |
| 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 | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Zykadia (ceritinib) in culture (PMID: 38448512). | 38448512 |
| 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 | 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 | 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... |
| EML4 - ALK ALK L1196M ALK G1202R | lung non-small cell carcinoma | predicted - sensitive | NUV-655 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, NUV-655 demonstrated activity in a patient-derived non-small cell lung cancer cell line harboring EML4-ALK with ALK G1202R and ALK L1196M in culture and induced tumor regression in a patient-derived xenograft (PDX) model (Eur J Cancer 2022 Vol 174, Supp 1:S78-S79). | detail... |
| EML4 - ALK ALK L1196M ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1196M and ALK G1202R were identified in the post-progression circulating tumor DNA of a patient with non-small cell lung cancer harboring EML4-ALK who progressed on treatment with Alunbrig (brigatinib), and in a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Alunbrig (brigatinib) in culture (PMID: 38448512, PMID: 36806896). | 36806896 38448512 |
| ALK rearrange ALK G1202R ALK G1269A | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R ALK G1269A developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). | 29650534 |
| ALK rearrange ALK 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 and ALK L1196M developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 29650534). | 29650534 |
| ALK rearrange ALK L1196M ALK G1202R | lung non-small cell carcinoma | resistant | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is not indicated for use as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK L1196M and G1202R compound mutations (NCCN.org). | detail... |
| ALK rearrange ALK G1202R ALK L1204V ALK G1269A | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, ALK G1269A and L1204V were identified as acquired mutations in an ALK-positive non-small cell lung cancer patient harboring ALK G1202R who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). | 29650534 |
| ALK rearrange ALK 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 fusion ALK G1202R KIT amp | lung non-small cell carcinoma | predicted - resistant | 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 |
| ALK rearrange ALK F1174L ALK G1202R | lung non-small cell carcinoma | predicted - resistant | 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 | 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 | 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 G1202R 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 33% (2/6, all partial responses) and stable disease in 50% (3/6) of patients with ALK-positive non-small cell lung cancer harboring ALK G1202R (PMID: 31628085; NCT0321569). | 31628085 |
| EML4 - ALK ALK E1154K ALK G1202R ALK I1268V | lung adenocarcinoma | predicted - resistant | 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 E1154K ALK G1202R ALK I1268V | lung adenocarcinoma | predicted - resistant | 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 T1151M ALK C1156Y ALK F1174L ALK G1202R ALK S1206F ALK G1269A | lung adenocarcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 3.7 months therapy in a patient with lung adenocarcinoma harboring EML4-ALK and ALK G1202R, at disease progression, ALK F1174L in cis wth ALK G1202R was identified in biopsies, and ALK C1156Y, G1269A, S1206F, and T1151M were identified in ctDNA (PMID: 31585938). | 31585938 |
| EML4 - ALK ALK F1174L ALK G1202R | Advanced Solid Tumor | resistant | 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 |
| EML4 - ALK ALK C1156Y ALK G1202R | 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 G1202R compound mutation in the context of EML4-ALK in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK C1156Y ALK G1202R | Advanced Solid Tumor | sensitive | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, TPX-0131 treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK G1202R and C1156Y in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK C1156Y ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and ALK C1156Y compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK C1156Y ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and C1156Y were resistant to Xalkori (crizotinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK C1156Y ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and ALK C1156Y compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK C1156Y ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and C1156Y were resistant to Alecensa (alectinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK C1156Y ALK G1202R | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK C1156Y and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK C1156Y ALK G1202R | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and C1156Y compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK C1156Y ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and C1156Y compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK C1156Y ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and C1156Y were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK C1156Y ALK G1202R | Advanced Solid Tumor | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and C1156Y were resistant to Xospata (gilteritinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | sensitive | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | predicted - sensitive | NUV-655 | Preclinical - Cell culture | Actionable | In a preclinical study, NUV-655 treatment resulted in decreased cell growth in a cell line expressing EML4-ALK fusion and ALK mutations, G1202R and G1269A, in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1468). | detail... |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK G1269A were resistant to Xalkori (crizotinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK G1269A were resistant to Alecensa (alectinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1269A and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK G1202R ALK L1204V ALK G1269A | Advanced Solid Tumor | sensitive | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1202R, ALK L1204V, and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R ALK L1204V ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R ALK L1204V ALK G1269A | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, G1269A, and L1204V compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R ALK L1204V ALK G1269A | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1269A, L1204V, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R ALK L1204V ALK G1269A | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R ALK L1204V ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | sensitive | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F, ALK G1202R, and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, G1269A, and L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1269A, L1198F, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK V1180L ALK G1202R | large cell neuroendocrine carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK developed progressive disease after initial response to Alecensa (alectinib) treatment, post-progression circulating tumor DNA analysis identified the acquisition of ALK V1180L and ALK G1202R, together with TP53 G105V and MYCN E378fs (PMID: 34994612). | 34994612 |
| EML4 - ALK ALK V1180L ALK G1202R | large cell neuroendocrine carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK and acquired ALK V1180L and ALK G1202R mutations demonstrated further progressive disease 2 weeks after initiating Alunbrig (brigatinib) treatment (PMID: 34994612). | 34994612 |
| EML4 - ALK ALK V1180L ALK G1202R | large cell neuroendocrine carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in clinical improvement and regression of lung lesions after 4 weeks of therapy in a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK and acquired ALK V1180L and ALK G1202R mutations; however, new bone lesions and progression of the brain mass was seen, and significant progressive disease developed after 3 months (PMID: 34994612). | 34994612 |
| 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 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 |
| 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 |
| EML4 - ALK ALK G1202R ALK S1206F | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Xalkori (crizotinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK G1202R ALK S1206F | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Zykadia (ceritinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK G1202R ALK S1206F | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Alecensa (alectinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK G1202R ALK S1206F | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Alunbrig (brigatinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK G1202R ALK S1206F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK G1202R ALK S1206F ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Xalkori (crizotinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK G1202R ALK S1206F ALK G1269A | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, S1206F, and G1269A were resistant to Zykadia (ceritinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK G1202R ALK S1206F ALK G1269A | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Alecensa (alectinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK G1202R ALK S1206F ALK G1269A | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Alunbrig (brigatinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK G1202R ALK S1206F ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK T1151K ALK G1202R ALK S1206F | lung adenocarcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK S1206F and ALK T1151K were identified in a patient with lung adenocarcinoma harboring EML4-ALK (e6a:e20) and ALK G1202R after the disease progressed on Lorbrena (lorlatinib) treatment (PMID: 35328235). | 35328235 |
| 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 |
| ALK fusion ALK G1202R ALK L1204V ALK G1269A | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1204V and ALK G1269A were identified as acquired mutations in a non-small cell lung cancer patient harboring an ALK fusion with ALK G1202R who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). | 35726063 |
| ALK fusion ALK G1202R ALK S1206F ALK G1269A | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK S1206F and ALK G1269A were identified as acquired mutations in a non-small cell lung cancer patient harboring an ALK fusion with ALK G1202R who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK L1196M ALK G1202R ALK D1203N | large cell neuroendocrine carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1196M, ALK D1203N, and ALK G1202R were identified on post-progression biopsy in a patient with metastatic large cell neuroendocrine lung carcinoma harboring EML4-ALK (e20:e20), who previously achieved disease stabilization for 8 months with Lorbrena (lorlatinib) treatment (PMID: 36207130). | 36207130 |
| EML4 - ALK ALK E1129V ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and E1129V were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK E1129V ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and E1129V were resistant to Xalkori (crizotinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK E1129V ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and E1129V were resistant to Alecensa (alectinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK E1129V ALK G1202R | Advanced Solid Tumor | sensitive | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, TPX-0131 treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK G1202R and E1129V in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK E1129V ALK G1202R | Advanced Solid Tumor | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and E1129V were resistant to Xospata (gilteritinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK F1174C ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK F1174C ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to Xalkori (crizotinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK F1174C ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to Alecensa (alectinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK F1174C ALK G1202R | Advanced Solid Tumor | resistant | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to TPX-0131 in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK F1174C ALK G1202R | Advanced Solid Tumor | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to Xospata (gilteritinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK F1174I ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK F1174I ALK G1202R | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Xalkori (crizotinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK F1174I ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Alecensa (alectinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK F1174I ALK G1202R | Advanced Solid Tumor | resistant | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to TPX-0131 in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK F1174I ALK G1202R | Advanced Solid Tumor | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Xospata (gilteritinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK T1151M ALK G1202R | lung non-small cell carcinoma | predicted - sensitive | NUV-655 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, NUV-655 demonstrated activity in a patient-derived non-small cell lung cancer cell line harboring EML4-ALK with ALK G1202R and ALK T1151M in culture and induced tumor regression in a patient-derived xenograft (PDX) model (Eur J Cancer 2022 Vol 174, Supp 1:S78-S79). | detail... |
| EML4 - ALK ALK I1171N ALK G1202R | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a lung adenocarcinoma patient harboring EML4-ALK with ALK I1171N and G1202R, along with ALK-ENC1 (PMID: 37007089). | 37007089 |
| ALK G1202R ALK R1275Q | neuroblastoma | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a neuroblastoma cell line harboring ALK R1275Q and expressing G1202R was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298). | 37147298 |
| ALK G1202R ALK R1275Q BRAF V600E | neuroblastoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a neuroblastoma patient harboring ALK R1275Q developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired ALK G1202R and BRAF V600E via circulating tumor DNA (PMID: 37147298; NCT03107988). | 37147298 |
| ALK F1174L ALK G1202R ALK D1203N ALK amp | neuroblastoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a neuroblastoma patient harboring ALK F1174L developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired ALK amplification, and ALK G1202R and D1203N each in cis with F1174L via circulating tumor DNA (PMID: 37147298; NCT03107988). | 37147298 |
| ALK F1174L ALK G1202R | neuroblastoma | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a neuroblastoma cell line harboring ALK F1174L and expressing G1202R was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298). | 37147298 |
| ALK G1202R ALK D1276_R1279delinsE | neuroblastoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, a neuroblastoma patient harboring ALK D1276_R1279delinsE developed progressive disease on treatment with Xalkori (crizotinib) and was found to have acquired ALK G1202R via circulating tumor DNA (PMID: 37147298). | 37147298 |
| ALK G1202R ALK D1276_R1279delinsE | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a complete metabolic response and a partial anatomic response in a neuroblastoma patient harboring ALK D1276_R1279delinsE and G1202R, who remained on the treatment for over 27 cycles (PMID: 37147298; NCT03107988). | 37147298 |