RC48 Plus Bevacizumab or Pyrotinib in HER2-Positive Metastatic Breast Cancer After T-DXd Failure: A Phase II Study

Inclusion Criteria: 1. Age ≥18 years. 2. Histologically or cytologically confirmed HER2-positive (IHC 3+ or IHC 2+ with ISH amplification) advanced or metastatic breast cancer. 3. Prior treatment with trastuzumab deruxtecan (T-DXd) and documented disease progression during or after therapy. 4. At least one measurable lesion at baseline as defined by RECIST v1.1. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Adequate organ and marrow function, including: Absolute neutrophil count ≥1.5 × 10⁹/L Platelet count ≥100 × 10⁹/L Hemoglobin ≥9 g/dL ALT and AST ≤2.5 × ULN Total bilirubin ≤1.5 × ULN Creatinine clearance ≥50 mL/min Estimated life expectancy of ≥12 weeks. Ability to understand and willingness to sign a written informed consent form. Exclusion Criteria: 1. Prior treatment with disitamab vedotin (RC48). 2. Active infections requiring systemic therapy (bacterial, viral, or fungal). 3. History of interstitial lung disease or non-infectious pneumonitis requiring corticosteroid therapy. 4. Uncontrolled cardiovascular disease, including but not limited to: uncontrolled hypertension, recent myocardial infarction (within 6 months), unstable angina, or congestive heart failure. 5. Pregnant or breastfeeding women. 6. Concurrent malignancy other than adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix, unless disease-free for ≥5 years. 7. Participation in another interventional clinical trial with investigational agents not yet completed. 8. Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements or jeopardize their safety.