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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 has been demonstrated to confer drug resistance in the context of ALK fusions (PMID: 22277784, PMID: 24736079), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2021). |
| Associated Drug Resistance | Y |
| Transcript | NM_004304.4 |
| 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 | chr2:g.29220747C>T | c.3604G>A | p.G1202R | RefSeq | GRCh38/hg38 |
| NM_004304.4 | 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 |
|---|---|---|---|---|---|---|---|
| ALK G1202R | Advanced Solid Tumor | sensitive | Repotrectinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Repotrectinib (TPX-0005) inhibited ALK G1202R and suppressed tumor growth in cell line xenograft models with ALK G1202R (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). | detail... |
| 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, 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 | 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 | lung cancer | conflicting | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorlatinib (PF-06463922) 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 | predicted - sensitive | TPX-0131 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture, and inhibited tumor growth in a cell line xenograft model (AACR Virtual Annual Meeting II (Jun 2020), Abstract 52226). | detail... |
| 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 | 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 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 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 treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK G1202R | lung adenocarcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted disease progression after 2.5 months of therapy 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, only ALK G1202R with increased allelic frequency was detected at disease progression (PMID: 31585938). | 31585938 |
| 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 | 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 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 | 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, Repotrectinib (TPX-0005) inhibited Alk activity and proliferation of transformed cells expressing ALK G1201R in the context of EML4-ALK in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 30093503). | 30093503 detail... |
| 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 | 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 | 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 | 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 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 |
| 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 G1202R | Advanced Solid Tumor | predicted - 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 inhibited tumor growth in a cell line xenograft model (AACR Virtual Annual Meeting II (Jun 2020), Abstract 52226). | detail... |
| 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 | Lorlatinib is included in guidelines as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK G1202R (NCCN.org). | detail... |
| ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | 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 | 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 | 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 | 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 | 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 | 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 |
| 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 | 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, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK L1196M ALK G1202R | Advanced Solid Tumor | resistant | 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 | predicted - 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 inhibited tumor growth in a cell line xenograft model (AACR Virtual Annual Meeting II (Jun 2020), Abstract 52226). | detail... |
| 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 | 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 | 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 | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK L1196M ALK G1202R | Advanced Solid Tumor | resistant | 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 | predicted - resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). | 33627640 |
| 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 ALK L1196M developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). | 29650534 |
| ALK rearrange ALK G1202R ALK L1204V ALK G1269A | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, ALK G1269A and L1204V were identified as acquired mutations in an ALK-positive non-small cell lung cancer patient harboring ALK G1202R who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). | 29650534 |
| ALK rearrange ALK 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 | predicted - 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 (AACR Virtual Annual Meeting II (Jun 2020), Abstract 52226). | detail... |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | predicted - 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 (AACR Virtual Annual Meeting II (Jun 2020), Abstract 52226). | detail... |
| 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 G1296A, in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1468). | detail... |
| EML4 - ALK ALK G1202R ALK L1204V ALK G1269A | Advanced Solid Tumor | predicted - 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 (AACR Virtual Annual Meeting II (Jun 2020), Abstract 52226). | detail... |
| EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | predicted - 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 (AACR Virtual Annual Meeting II (Jun 2020), Abstract 52226). | detail... |