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Background: The effect of the combination of an anti-angiogenic agent with a poly (ADP-ribose) polymerase (PARP) inhibitor in cancer treatment is unclear. We assessed the oral combination of fuzuloparib, a PARP inhibitor, and apatinib, a VEGFR2 inhibitor for treating advanced ovarian cancer (OC) or triple-negative breast cancer (TNBC). Methods: This dose-escalation and pharmacokinetics-expansion phase 1 trial was conducted in China. We used a standard 3 + 3 dose-escalation design, with 7 dose levels tested. Patients received fuzuloparib orally twice daily, and apatinib orally once daily. The study objectives were to determine the safety profile, recommended phase 2 dose (RP2D), pharmacokinetics, preliminary efficacy, and efficacy in relation to germline BRCA mutation (gBRCAmut). Results: Fifty-two pre-treated patients were enrolled (30 OC/22 TNBC). 5 (9.6%) patients had complete response, 14 (26.9%) had partial response, and 15 (28.8%) had stable disease. Objective response rate (ORR) and disease control rate were 36.5% (95% CI 23.6–51.0) and 65.4% (95% CI 50.9–78.0), respectively. At the highest dose level of fuzuloparib 100 mg plus apatinib 500 mg, the ORR was 50.0% (4/8; 95% CI 15.7–84.3); this dose was determined to be the RP2D. Patients with gBRCAmut had higher ORR and longer median progression-free survival (PFS) than those with gBRCAwt, both in OC (ORR, 62.5% [5/8] vs 40.9% [9/22]; PFS, 9.4 vs 6.7 months) and TNBC (ORR, 66.7% [2/3] vs 15.8% [3/19]; PFS, 5.6 vs 2.8 months). Two dose-limiting toxicities occurred: grade 4 febrile neutropenia (fuzuloparib 100 mg plus apatinib 250 mg) and thrombocytopenia (fuzuloparib 100 mg plus apatinib 375 mg). Maximum tolerated dose was not reached. The most common treatment-related grade ≥ 3 toxicities in all patients were hypertension (19.2%), anaemia (13.5%), and decreased platelet count (5.8%). Exposure of apatinib increased proportionally with increasing dose ranging from 250 to 500 mg, when combined with fuzuloparib 100 mg. Conclusions: Fuzuloparib plus apatinib had acceptable safety in patients with advanced OC or TNBC. Fuzuloparib 100 mg bid plus apatinib 500 mg qd was established as the RP2D. With the promising clinical activity observed, this combination is warranted to be further explored as a potential alternative to chemotherapy. Trial registration: ClinicalTrials.gov, NCT03075462 (Mar. 9, 2017). [ABSTRACT FROM AUTHOR]

Famitinib is a tyrosine kinase inhibitor under clinical investigation for the treatment of solid tumors. Here, a 3‐period crossover trial investigated the effect of high‐fat or low‐fat food intake on the single‐dose pharmacokinetic properties of oral famitinib. Twenty‐four healthy Chinese participants were enrolled and received a single 25‐mg dose of famitinib malate capsule following a high‐fat or low‐fat breakfast before dosing. Blood samples were collected before dosing (0 hour) to 192 hours after dosing, and famitinib concentrations in plasma were determined with validated liquid chromatography–tandem mass spectrometry. Compared with the fasting condition, the geometric mean ratios for low‐fat/fasting were 98.6%, 107.7%, and 107.5% for maximum plasma concentration, area under the plasma concentration–time curve (AUC) over the dosing interval, and AUC from time 0 to infinity, respectively. Those for high‐fat/fasting were 84.4%, 105.0%, and 105.1% for maximum plasma concentration, AUC over the dosing interval, and AUC from time 0 to infinity, respectively. There was no significant difference in adverse events between fasting and fed conditions, and no serious adverse events occurred during the trial. In conclusion, oral famitinib bioavailability is not affected by food intake, implying that patients with cancer do not need to consider dietary status when using famitinib. This is considered important for convenience and treatment compliance. [ABSTRACT FROM AUTHOR]