Serplulimab Combined With Trastuzumab Rezetecan as Neoadjuvant Therapy for Triple-Negative Breast Cancer

Prior treatment

• Prior systemic anticancer therapy (including chemotherapy, endocrine therapy, immunotherapy, or biological therapy) for any malignancy within 4 weeks before the first dose of study treatment.

Other illness

• Evidence of metastatic (Stage IV) disease or bilateral breast cancer at diagnosis.
• Diagnosis of any other malignancy within the past 5 years, except for adequately treated non-melanoma skin cancer, basal cell carcinoma, or carcinoma in situ of the cervix.
• Known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV-DNA ≥500 IU/mL), or hepatitis C virus (detectable HCV-RNA).
• Active autoimmune disease requiring systemic immunosuppressive therapy within the past 2 years.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic antibiotic therapy within 2 weeks, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements.
• History of allogeneic hematopoietic stem cell or solid organ transplantation.
• Known hypersensitivity to any component of serplulimab or SHR-A1811.
• Any condition that, in the opinion of the investigator, would compromise patient safety or interfere with the completion of the study procedures.

Other

• Pregnant or lactating women, or women of childbearing potential who are unwilling to use a highly effective method of contraception during the treatment period and for at least 7 months after the last dose.

• Female patients aged 18 to 70 years, inclusive.
• Histologically confirmed, treatment-naïve, early-stage triple-negative breast cancer (TNBC), defined as estrogen receptor (ER) and progesterone receptor (PR) expression \<1% by immunohistochemistry (IHC), and human epidermal growth factor receptor 2 (HER2)-negative (IHC 0/1+ or IHC 2+ with negative in situ hybridization confirmation) per current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.
• Clinical stage T1cN1-2 or T2-4N0-2 according to the American Joint Committee on Cancer (AJCC) staging system, 8th edition.
• At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematologic, hepatic, renal, and cardiac function within 14 days prior to enrollment:
  • Hematologic: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; platelet count ≥100 × 10⁹/L; hemoglobin ≥90 g/L (without transfusion or growth factor support within 14 days).
  • Hepatic: Total bilirubin ≤1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN.
  • Renal: Serum creatinine and blood urea nitrogen (BUN) ≤1.5 × ULN.
  • Cardiac: Left ventricular ejection fraction (LVEF) ≥50% measured by echocardiogram; corrected QT interval (QTc) \<470 ms on 12-lead electrocardiogram (ECG).
• Willingness to provide archival or fresh tumor tissue sample for programmed death-ligand 1 (PD-L1) biomarker analysis using the 22C3 pharmDx assay.
• Ability to understand and willingness to sign a written informed consent document.