Efficacy and Safety of Ripretinib in Chinese Patients with Advanced Gastrointestinal Stromal Tumors as a Fourth- or Later-Line Therapy: A Multicenter, Single-Arm, Open-Label Phase II Study

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 sur-vival (PFS) based on independent radiologic review (IRR). Second-ary 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 clin-ically 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.