Imatinib is an effective first-line treatment for pts with adv GIST; however, most pts inevitably relapse or progress. Approved second- and third-line agents, sunitinib and regorafenib, have shown limited activity/tolerability, defining an unmet need for pts with imatinib-resistant GIST. Avapritinib is a highly potent and selective oral kinase inhibitor that targets mutant forms of KIT and PDGFRA, including those that confer resistance to approved tyrosine kinase inhibitors. In the Phase 1 NAVIGATOR study (NCT02508532), avapritinib showed substantial clinical activity in pts with both KIT- and PDGFRA-mutant GIST that was resistant to all available therapies. Based on these findings, the VOYAGER study was initiated, comparing avapritinib with regorafenib in pts with adv GIST.
VOYAGER (NCT03465722), an international, multicentre, open-label, randomised, Phase 3 study, will include pts (aged ≥18; ECOG PS 0–2) with locally adv metastatic or unresectable GIST. The study will evaluate avapritinib vs regorafenib in pts previously treated with imatinib and 1 or 2 other tyrosine kinase inhibitors, who have experienced disease progression, inadequate clinical benefit or intolerance to their prior therapy. Pts with GIST that is wild-type in both KIT and PDGFRA will be excluded. Approximately 460 pts will be enrolled across North America, Europe, Australia and Asia. Pts will be randomised 1:1 to receive avapritinib 300 mg orally, once daily (QD) or regorafenib 160 mg orally, QD (3 wks on/1 wk off), stratified by treatment regimen (third vs fourth), geographic region (Asia vs rest of the world) and mutation status (PDGFRα D842V present vs absent). Pts who experience disease progression on regorafenib, as confirmed by central radiology review, will be allowed to cross over to avapritinib. The primary objective is progression-free survival (PFS), based on central radiological assessment (mRECIST, v1.1). The study is designed to have 90% power to detect a hazard ratio of 0.67 (avapritinib vs regorafenib). Secondary objectives include evaluation of response rate, overall survival, health-related quality of life and safety.
Clinical trial identification
Legal entity responsible for the study
Blueprint Medicines Corporation.
Blueprint Medicines Corporation.
Samantha Clark from iMed Comms an Ashfield Company, part of UDG Healthcare plc, provided medical writing support funded by Blueprint Medicines Corporation.
S. Bauer: Grants and personal fees: Novartis, Blueprint Medicines; Personal fees: PharmaMar, Lilly, Deciphera; Grants: Incyte. S. George: Advisory boards: Deciphera Pharmaceuticals, Blueprint Medicines; Consultant: AstraZeneca. Y-K. Kang: Advisory role: BMS, Ono, Blueprint, Daehwa, LSK Biopharma, Novartis, Roche. W.D. Tap: Advisory boards and consultancy: Eli Lilly, EMD Serono, Novartis, Esai, Janssen, Immune Design, Adaptimmune, Daiichi Sankyo, Blueprint Medicines, Loxo. T. Zhou, A.L. Boral: Employee and stock options: Blueprint Medicines Corporation. N. Picazio: Employee of Blueprint Medicines Corporation. M. Heinrich: Consultancy: Novartis, Blueprint Medicines Corporation, Bayer, Deciphera, MolecularMD; Research funding: Blueprint Medicines, Deciphera; Equity interest: MolecularMD; Expert Testimony: Novartis.