Molecular Profile Detail

Profile Name NPM1-ALK
Gene Variant Detail

NPM1 NPM1 - ALK (gain of function)

Relevant Treatment Approaches ALK Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
NPM1-ALK anaplastic large cell lymphoma sensitive ALK Inhibitor Entrectinib Preclinical - Cell line xenograft Actionable In a preclinical study, anaplastic large cell lymphoma cells harboring NPM1-ALK were sensitive to Entrectinib (RXDX-101) in culture and in cell line xenograft models, resulting in inhibition of NPM1-ALK autophosphorylation and near complete tumor regression (PMID: 26939704). 26939704
NPM1-ALK Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK anaplastic large cell lymphoma sensitive ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of an anaplastic large cell lymphoma cell line harboring NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK anaplastic large cell lymphoma sensitive ALK Inhibitor CEP-28122 Preclinical - Pdx & cell culture Actionable In a preclinical study, CEP-28122 inhibited Alk activation, resulting in growth inhibition in culture, and tumor regression in both cell line and patient-derived xenograft models of NPM1-ALK positive anaplastic large cell lymphoma (PMID: 22203728). 22203728
NPM1-ALK Advanced Solid Tumor sensitive ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of transformed cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK Advanced Solid Tumor sensitive ALK Inhibitor TAE684 Preclinical - Cell culture Actionable In a preclinical study, TAE684 inhibited proliferation of transformed cells expressing NPM1-ALK in culture (PMID: 20207848). 20207848
NPM1-ALK anaplastic large cell lymphoma sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of an anaplastic large cell lymphoma cell line harboring NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing NPM1-ALK in culture (PMID: 25749034). 25749034
NPM1-ALK Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK anaplastic large cell lymphoma sensitive ALK Inhibitor Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alunbrig (brigatinib) inhibited Alk phosphorylation and growth in anaplastic large cell lymphoma cell lines harboring NPM1-ALK in culture, and induced near complete tumor regression in cell line xenograft models (PMID: 27780853). 27780853
NPM1-ALK Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK anaplastic large cell lymphoma sensitive ALK Inhibitor Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, Xalkori (crizotinib) inhibited cell growth, Alk phosphorylation, downstream signaling and induced apoptosis in human anaplastic large cell lymphoma cell lines harboring a NPM1-ALK fusion in culture and in xenograft models (PMID: 18089725). 18089725
NPM1-ALK anaplastic large cell lymphoma sensitive ALK Inhibitor Crizotinib Phase Ib/II Actionable In a Phase Ib/II trial, treatment with Xalkori (crizotinib) resulted in an objective response rate of 83% (5/6, all complete responses), at the 165 mg dose, and 90% (18/20, with complete response in 80% (16/20), at the recommended phase 2 dose of 280 mg, in patients with anaplastic large cell lymphoma harboring an ALK fusion, with 72% of tested patients harboring NPM1-ALK (PMID: 28787259; NCT00939770). 28787259
NPM1-ALK anaplastic large cell lymphoma sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of an anaplastic large cell lymphoma cell line harboring NPM1-ALK in culture (PMID: 25421750). 25421750
Clinical Trial Phase Therapies Title Recruitment Status