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Profile Name | ALK R1275Q |
Gene Variant Detail | |
Relevant Treatment Approaches | ALK Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK F1174L ALK R1275Q | neuroblastoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, and a patient harboring both ALK F1174L and ALK R1275Q stayed on treatment for 3 cycles until disease progression (PMID: 33568345; NCT00939770). | 33568345 |
EML4 - ALK ALK R1275Q | Advanced Solid Tumor | sensitive | TQ-B3139 | Preclinical - Cell culture | Actionable | In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of cells expressing EML4-ALK with ALK R1275Q in culture (PMID: 30210922). | 30210922 |
EML4 - ALK ALK R1275Q | Advanced Solid Tumor | sensitive | APG-2449 | Preclinical - Cell culture | Actionable | In a preclinical study, APG-2449 inhibited proliferation of cells expressing EML4-ALK with ALK R1275Q in culture (PMID: 35820889). | 35820889 |
ALK R1275Q TP53 wild-type | neuroblastoma | sensitive | Idasanutlin + TAE684 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of TAE684 and Idasanutlin (RG7388) inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 36602782). | 36602782 |
ALK R1275Q TP53 wild-type | neuroblastoma | sensitive | Alectinib + Idasanutlin | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 36602782). | 36602782 |
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 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 L1196M ALK R1275Q | neuroblastoma | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a neuroblastoma cell line harboring ALK R1275Q and expressing L1196M was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298). | 37147298 |
ALK R1275Q TP53 wild-type | neuroblastoma | sensitive | Ceritinib + CGM097 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Zykadia (ceritinib) and CGM097 inhibited Alk signaling and resulted in synergistic inhibition of proliferation in a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture and induced tumor regression in a cell line xenograft model (PMID: 28425916). | 28425916 |