A Single-Arm Phase Ⅱ Study of Fluzoparib Maintenance in Platinum-sensitive Advanced Triple-Negative Breast Cance

Breast cancer is the most common malignancy in women; approximately 5-10% are hereditary, with 14% of triple-negative breast cancers (TNBC) harboring BRCA mutations. BRCA1/2 are essential for homologous recombination repair of DNA double-strand breaks, whereas PARP mediates base-excision repair of single-strand breaks. PARP inhibitors (PARPi) exploit synthetic lethality to selectively eliminate BRCA-deficient tumor cells. Olaparib and talazoparib have demonstrated superior PFS and ORR versus chemotherapy in BRCA-mutated, HER2-negative advanced breast cancer, leading to FDA approval. In ovarian cancer, PARPi maintenance improves overall survival, with consistent benefits observed in Asian populations. The domestically developed PARPi fluzoparib, engineered with a trifluoromethyl moiety for enhanced stability and tissue penetration, showed in the phase III FABULOUS trial a median PFS of 6.7 vs 3.0 months and an ORR of 43.6% vs 23.3% compared with chemotherapy in gBRCA-mutated, HER2-negative breast cancer, with manageable safety. Data remain limited in Chinese patients and those with BRCA wild-type disease. This study aims to evaluate the efficacy and safety of fluzoparib maintenance monotherapy in advanced TNBC patients-either BRCA1/2-mutated or wild-type-who have derived clinical benefit from prior platinum-based therapy.

Inclusion Criteria: 1. Age 18-75 years (inclusive) at the time of informed consent. 2. Histologically confirmed triple-negative breast cancer (TNBC; ER \38.5 °C on screening or day 1 (tumor fever allowed if investigator judges stable). 19. Uncontrolled chronic systemic diseases (severe pulmonary, hepatic, renal, or cardiac). 20. Thyroid function abnormalities (TSH, FT3, FT4) deemed clinically significant by the investigator. 21. Bleeding diathesis: active peptic ulcer with positive fecal occult blood (FOB ++), melena or hematemesis within 2 months, or any condition predisposing to GI hemorrhage; gastric ulcer-type tumor without resection and judged at high risk of major bleeding; on thrombolytic/anticoagulant therapy that cannot be safely interrupted. 22. Urinalysis ≥++ proteinuria confirmed by 24-h urine protein \>1.0 g. 23. Arterial or venous thrombo-embolic events (stroke, TIA, DVT, PE) within 6 months before screening. 24. Active tuberculosis or acute infection requiring anti-infective therapy. 25. Live-vaccine administration within 30 days before planned first dose. 26. Additional exclusion: Any severe concomitant condition that, in the investigator's opinion, could compromise patient safety or interfere with study compliance (e.g., uncontrolled diabetes, thyroid disorders, psychiatric illness).