Background: The combination of an anti-angiogenic agent with a poly (ADP-ribose) polymerase (PARP) inhibitor has demonstrated improved clinical outcomes as treatment/maintenance treatment in gynecological cancers. Here we aimed to characterize the safety profile and recommended phase 2 dose (RP2D) of the combination of fuzuloparib (formerly fluzoparib), a PARP inhibitor, and apatinib, a VEGFR inhibitor in recurrent ovarian cancer (OC) or triple-negative breast cancer (TNBC). Methods: This was a dose-escalation and PK-expansion phase 1 trial conducted in China. Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer or metastatic TNBC were eligible. No prior PARP/VEGFR inhibitors were allowed. The study used a standard 3+3 dose-escalation design, with additional patients (a total of 8-12 patients per dose level) enrolled for PK assessment. Patients received orally a single dose of fluzoparib on D1 and apatinib on D4, followed by continuous dosing of fluzoparib (bid) plus apatinib (qd) starting on D8. Endpoints were RP2D, safety, PK, and anti-tumor activity. Results: Between 03/17/2017 and 03/02/2021, 52 patients (30 OC, 22 TNBC) were enrolled to 7 dose levels (up to fuzuloparib 100 mg plus apatinib 500 mg). A total of 2 DLTs occurred: grade 4 decreased white blood cell count (WBC)/febrile neutropenia (fuzuloparib 100 mg plus apatinib 250 mg) and grade 4 thrombocytopenia (fuzuloparib 100 mg plus apatinib 375 mg). No maximum tolerated dose was reached. The most common treatment-related grade ≥3 toxicities included hypertension, anemia/decreased hemoglobin, thrombocytopenia, and decreased WBC. In PK analysis, steady-state plasma concentrations of apatinib was decreased when combined with fuzuloparib, as compared with apatinib alone. Higher dose of apatinib in combination with fuzuloparib 100 mg was associated with higher exposure and improved clinical activity. The ORR was 44% (95% CI, 32-58; OC, 60% [95% CI, 42-75]; TNBC, 23% [95% CI, 10-43]) across all dose levels and 62.5% (95% CI, 31-86) at fuzuloparib 100 mg plus apatinib 500 mg (all OC), which was determined to be the RP2D. Conclusions: Fuzuloparib plus apatinib has acceptable safety in patients with recurrent ovarian cancer and triple-negative breast cancer. With the promising clinical activity observed in ovarian cancer, this combination is warranted to be further explored as a potential alternative to chemotherapy. Clinical trial information: NCT03075462.