Molecular Profile Detail

Profile Name PDGFRA D842V
Gene Variant Detail

PDGFRA D842V (gain of function)

Relevant Treatment Approaches PDGFR Inhibitor (Pan) PDGFR-alpha Inhibitor Avapritinib

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
PDGFRA D842V Advanced Solid Tumor resistant PDGFR Inhibitor (Pan) Sunitinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing PDGFRA D842V demonstrated resistance to inhibition of PDGFRA phosphorylation by Sutent (sunitinib) in culture (PMID: 18955458). 18955458
PDGFRA D842V gastrointestinal stromal tumor predicted - sensitive PDGFR Inhibitor (Pan) Dasatinib Phase 0 Actionable In a clinical trial, Sprycel (dasatinib) treatment resulted in a partial response in 25% (12/48) of patients with Gleevec (imatinib)-resistant gastrointestinal stromal tumor, with decreased tumor size in 2 of those patients, 1 of which harbored PDGFRA D842V (PMID: 29710216). 29710216
PDGFRA D842V Advanced Solid Tumor resistant PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, expression of PDGFRA D842V conferred resistance to Gleevec (imatinib) in cell culture (PMID: 15928335). 15928335
PDGFRA D842V Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited Pdgfra phosphorylation and proliferation of transformed cells expressing PDGFRA D842V in culture (PMID: 22745105). 22745105
PDGFRA D842V Advanced Solid Tumor resistant PDGFR Inhibitor (Pan) Nilotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing PDGFRA D842V demonstrated resistance to growth inhibition by Tasigna (nilotinib) in culture (PMID: 18794084). 18794084
PDGFRA D842V gastrointestinal stromal tumor sensitive PDGFR Inhibitor (Pan) Crenolanib Phase Ib/II Actionable In a Phase I/II trial, treatment with Crenolanib (CP-868596) resulted in a clinical benefit rate of 31% (5/16) in gastronintestinal stromal tumor patients harboring PDGFRA D842V, with partial response in 2/16 and stable disease in 3/16 patients (J Clin Oncol 34, 2016 (suppl; abstr 11010)). detail...
PDGFRA D842V Advanced Solid Tumor sensitive Avapritinib PDGFR-alpha Inhibitor Avapritinib Preclinical - Cell culture Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation in transformed cells overexpressing PDGFRA D842V in culture (PMID: 29093181). 29093181
PDGFRA D842V gastrointestinal stromal tumor sensitive Avapritinib PDGFR-alpha Inhibitor Avapritinib Phase I Actionable In a Phase I trial, BLU-285 treatment resulted in partial response lasted for more than 15 cycles of treatment, and sustained reduction of plasma PDGFRA D842V in a patient with gastrointestinal stromal tumor harboring PDGFRA D842V, whose disease had progressed on previous Gleevec (imatinib mesylate), Sprycel (dasatinib), and Crenolanib treatment (PMID: 29093181; NCT02508532). 29093181
PDGFRA D842V gastrointestinal stromal tumor predicted - sensitive PDGFR Inhibitor (Pan) Regorafenib Clinical Study Actionable In a clinical study, Stivarga (regorafenib) treatment resulted in partial response in 11% (2/18) of patients and stable disease in 39% (7/18) of gastrointestinal stromal tumor patients, including prolonged stable disease for 12 months in a patient harboring PDGFRA D842V (PMID: 25905001). 25905001
Clinical Trial Phase Therapies Title Recruitment Status
NCT02847429 Phase III Crenolanib Randomized Trial of Crenolanib in Subjects With D842V Mutated GIST Recruiting