Additional Details of Endpoints or Study Design
Tumors, tumor, DLTs, unresectable GIST
TUMOR, TUMORS, GIST, ONCOLOGY, APPENDIX
Phase I used a modified 3 + 3 dose-escalation design for safety and phase II dose determination.Phase II was a dose-expansion phase for safety and efficacy evaluation. Screening, follow-up, and procedure details are described in the Appendix. This study was initiated in August 2019 and registered with ClinicalTrials.gov, identifier: NCT04254939.Eligible Chinese patients were ≥18 years of age and had confirmed unresectable or metastatic GIST, at least one measurable lesion defined by the modified Response Evaluation Criteria in Solid Tumors (mRECIST v1.1) for patients with GIST, and an Eastern Cooperative Oncology Group performance status of 0-1. All patients provided written informed consent before study participation.In phase I, avapritinib was administered orally at a starting dose of 200 mg once daily (QD) for one or more cycles, each consisting of 28 consecutive days. After at least 3 evaluable patients in the first cohort completed the first cycle, DLTs were evaluated; dose escalation to 300 mg QD was based on the available safety data.For phase I/II, enrollment criteria were unresectable or metastatic GIST confirmed by histology or cytology; either progression after treatment with imatinib and at least one other tyrosine kinase inhibitor (TKI), intolerance, or lack of available standard of care (SOC); and a tumor harboring a mutation in the PDGFRA gene that results in a D842V substitution at the protein level.The phase II study included 2 cohorts: cohort 1 included patients with unresectable GIST harboring a PDGFRA D842V mutation; cohort 2 included patients with unresectable GIST having received at least 3 lines of therapy and without a PDGFRA D842V mutation.