Procedure
toxicity
DISEASE PROGRESSION
The study used a standard 3 + 3 dose escalation design. The starting dose of fuzuloparib was 40 mg twice daily (bid) in combination with a fixed dose of apatinib at 250 mg once daily (qd); fuzuloparib could be dose escalated in 20 mg increments to up to 100 mg. An additional dose level of fuzuloparib 80 mg bid plus apatinib 375 mg qd was planned after assessment of the regimen of fuzuloparib 80 mg bid plus apatinib 250 mg qd. If dose escalation of fuzuloparib to 100 mg was completed, dose escalation for apatinib was initiated with two dose level planned: 375 mg qd and 500 mg qd (with fuzuloparib fixed at 100 mg bid). During dose escalation, the next-higher dose level was opened if less than one-third of patients in the previous dose level experienced a dose-limiting toxicity (DLT). Based on preliminary safety and efficacy data in the dose-escalation cohort, dose levels for PK-expansion were selected, with a total of 8–12 patients enrolled in each level. All patients received a single dose of oral fuzuloparib on day 1 and a single dose of oral apatinib on day 4 in cycle 0 (6 days in total), followed by continuous dosing of fuzuloparib and apatinib in 28-day cycles starting on cycle 1 day 1. Treatment continued until disease progression, intolerable toxicity, or patient withdrawal.