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

Prior treatment

• Prior treatment with any PARP inhibitor.
• Use of strong CYP3A4 inhibitors within 14 days or strong CYP3A4 inducers within 28 days before first dose.
• Wash-out interval \<4 weeks from any prior anti-cancer therapy (chemotherapy, radiotherapy, surgery, targeted therapy, immunotherapy) to first dose.
• Symptomatic or untreated brain metastases, leptomeningeal disease, spinal cord compression, or primary CNS tumors. (Stable brain metastases treated ≥28 days prior to first dose, without steroids and with confirmatory imaging showing no hemorrhage, may be allowed at investigator's discretion.)
• Recovery from major surgery under general anesthesia or severe trauma \<14 days before start of study treatment.
• History of immunodeficiency (including HIV positive), congenital or acquired, or prior solid-organ transplant.
• Alcohol abuse (\>14 units/week) or drug abuse; inability to stop smoking (\>10 cigarettes/day), nicotine products, grapefruit juice, or excessive caffeine/tea during the study.
• Arterial or venous thrombo-embolic events (stroke, TIA, DVT, PE) within 6 months before screening.
• Live-vaccine administration within 30 days before planned first dose.
• 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).

Other illness

• Known hypersensitivity to fluzoparib or any of its excipients.
• Planned anti-cancer therapy other than study drug during the trial period.
• Active autoimmune disease requiring systemic therapy within the past 2 years.
• Other malignancies within 5 years except adequately treated carcinoma in situ or indolent tumors judged by the investigator to have low risk of recurrence.
• History of non-infectious pneumonitis requiring steroids or current pneumonitis.
• Conditions that could impair oral absorption: inability to swallow, active GI disease, bowel obstruction, inflammatory bowel disease, chronic diarrhea, short-bowel syndrome, or major upper-GI surgery (e.g., gastrectomy).
• Active infection or unexplained fever \>38.5 °C on screening or day 1 (tumor fever allowed if investigator judges stable).
• Uncontrolled chronic systemic diseases (severe pulmonary, hepatic, renal, or cardiac).
• 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.
• Active tuberculosis or acute infection requiring anti-infective therapy.

Lab values

• Active hepatitis B (HBsAg positive and HBV DNA ≥500 IU/mL) or hepatitis C (anti-HCV positive and HCV RNA \>ULN).
• Clinically significant ECG abnormalities, including QTcF \>470 ms in females (QTc calculated with Fredericia's formula).

Other

• Severe bone complications from bone metastases (uncontrolled pain, impending pathological fracture, or spinal cord compression within 6 months or judged likely to occur).
• Untreated CNS metastases.
• Thyroid function abnormalities (TSH, FT3, FT4) deemed clinically significant by the investigator.
• Urinalysis ≥++ proteinuria confirmed by 24-h urine protein \>1.0 g.

• Age 18-75 years (inclusive) at the time of informed consent.
• Histologically confirmed triple-negative breast cancer (TNBC; ER \<1%, PR \<1%, HER2-negative).
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Received ≥2 prior lines of systemic therapy, including a platinum-based regimen (single-agent or combination); must have achieved partial response (PR) or stable disease (SD) during or after that platinum-based treatment.
• Platinum-sensitive disease defined as: Objective response (complete or partial) or stable disease lasting ≥6 months while on platinum-based therapy, or Platinum-free interval (PFI) ≥6 months from the end of the last platinum-containing regimen to documented progression/relapse.
• Estimated life expectancy ≥3 months.
• At least one measurable lesion per RECIST 1.1 on CT/MRI; evidence of metastatic disease (soft-tissue and/or bone lesions) is required.
• Willing to provide archived tumour tissue (core biopsy or excision) or fresh biopsy/blood for biomarker analyses.
• Adequate organ function within 14 days (7 days for liver enzymes) before first dose:
  • Absolute neutrophil count ≥1.5 × 10⁹/L Platelets ≥100 × 10⁹/L Haemoglobin ≥80 g/L Total bilirubin ≤1.5 × upper limit of normal (ULN) ALT \& AST ≤2.5 × ULN (≤5 × ULN if liver metastases present) Serum creatinine ≤1.25 × ULN and calculated creatinine clearance ≥60 mL/min
• Toxicities from prior anti-cancer therapy resolved to Grade ≤1 per NCI-CTCAE v5.0 (except alopecia or other stable chronic toxicities deemed tolerable by the investigator).
• Participants of reproductive potential and their partners must agree to use highly effective contraception from 30 days before the first dose until 120 days after the last dose of fluzoparib.
• Signed written informed consent prior to any study-specific procedures.