Study of JSKN016 Combination Therapy in Inoperable Locally Advanced or Metastatic HER2-Negative Breast Cancer

Inclusion Criteria: 1. Capable of understanding and signing the informed consent form. 2. Aged ≥18 and ≤75 years, regardless of sex. 3. Histologically or cytologically confirmed inoperable locally advanced or metastatic HER2-negative breast cancer. 4. Hormone receptor-positive participants with progression/intolerance after standard endocrine therapy, or unsuitable for it. 5. Disease progression confirmed by radiological evidence post-systemic treatment. 6. Available archived or newly obtained tumor tissue/biopsy. 7. No prior systemic therapy for advanced disease, except for prior endocrine ± targeted therapy or CDK4/6 inhibitors. 8. Measurable non-CNS lesion per RECIST 1.1. 9. Expected survival ≥3 months. 10. ECOG performance status of 0 or 1. 11. Contraceptive use agreement for fertile participants. 12. Adequate organ function within 7 days of enrollment: * Bone marrow: ANC ≥1.5 × 10⁹/L, Hemoglobin ≥90 g/L, Platelets ≥100 × 10⁹/L. * Liver: Bilirubin ≤1.5 × ULN, ALT/AST ≤3 × ULN. * Renal: Creatinine ≤1.5 × ULN or Ccr ≥60 mL/min. * Coagulation: INR/PT ≤1.5 × ULN, APTT ≤1.5 × ULN. 13. LVEF ≥50%. Exclusion Criteria: 1. CNS metastasis (except stable cases treated with radiation or surgery). 2. Unstable spinal cord compression or untreated history. 3. Recent live vaccine (except seasonal flu vaccines). 4. Recent anti-tumor treatment within 28 days or 5 half-lives (whichever is shorter). 5. Recent palliative therapy within 14 days. 6. Major surgery within 28 days or planned during the study. 7. Severe gastrointestinal issues or recent major GI bleeding. 8. Uncontrolled pleural/peritoneal effusions or cachexia. 9. Prior HER3/TROP2-targeted therapy or topoisomerase I inhibitors. 10. Other malignancies within 5 years (except certain skin or localized cancers). 11. Current interstitial lung disease or uncontrolled infections. 12. Severe hypercalcemia or uncontrolled cancer-related pain. 13. Autoimmune diseases, unless stable with treatment. 14. Uncontrolled comorbidities (e.g., active infections, cardiovascular issues). 15. Toxicities from previous treatments not resolved to CTCAE ≤1. 16. Recent steroid use or need for systemic immunosuppressive therapy. 17. Allergy to study drug components. 18. Pregnancy or breastfeeding.