Abstract
PURPOSE: This is a phase II multicenter, single-arm, open-label study assessing the efficacy, safety, and pharmacokinetics (PK) of ripretinib in Chinese patients with advanced gastrointestinal stromal tumor (GIST) as a fourth- or later-line therapy. It was designed to show consistency with the phase III INVICTUS study. PATIENTS AND METHODS: Patients with disease progression on (or intolerance to) prior imatinib, sunitinib, and at least one other drug were recruited to receive ripretinib 150 mg once daily continuously in 28-day cycles. The primary endpoint was progression-free survival (PFS) based on independent radiologic review (IRR). Secondary efficacy endpoints included objective response rate (ORR) based on IRR and overall survival. Safety endpoints included the incidence and severity of adverse events (AE). RESULTS: Between April 2020 and August 2020, 39 patients were enrolled. All were included in the safety analysis while 38 were included in the efficacy analysis. By primary data cut-off (February 26, 2021), the median PFS [90% confidence interval (CI)] was 7.2 (2.9-7.3) months; the lower bound of the 90% CI exceeded 1 month, fulfilling the standard of bridging success. The ORR (95% CI) based on IRR was 18.4% (7.7%-34.3%). Treatment-related treatment-emergent AEs (TRAE) were reported in 37 (94.9%) patients. The majority of TRAEs were of grade 1/2. A total of 6 patients (15.4%) experienced grade 3/4 TRAEs. CONCLUSIONS: The results demonstrated that ripretinib can clinically improve the outcomes of Chinese patients with advanced GIST as a fourth- or later-line therapy. The efficacy, safety, and PK profiles of ripretinib are consistent with those in the global patient population.