SHR-A2102 Combined With Adebrelimab as Neoadjuvant Therapy for Early Triple-Negative Breast Cancer

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• 3.1 Inclusion Criteria
• Subjects must meet all of the following criteria to be eligible:
• Age and gender: Female, ≥18 years old.
• Histopathological confirmation:
• Invasive breast cancer confirmed by histopathology.
• No prior systemic anti-tumor therapy for breast cancer.
• Triple-negative PD-L1-positive breast cancer:
• ER/PR-negative (IHC nuclear staining <10%).
• HER2-negative (IHC 0/1+ without FISH testing or IHC 2+ with FISH-negative amplification).
• PD-L1 Combined Positive Score (CPS) ≥1.
• Tumor stage: T1c-T2, N0-1 or T1a-T1b, N1 (per AJCC 8th Edition criteria).
• Measurable lesion: At least one measurable target lesion per RECIST v1.1.
• ECOG performance status: 0-1.
• Life expectancy: ≥3 months.
• Adequate organ and bone marrow function (within 1 month prior to treatment, without corrective therapy within 14 days before first dose):
• Bone marrow:
• Absolute neutrophil count (ANC) ≥2.0 ×10\^9/L.
• Platelets ≥100 ×10\^9/L.
• Hemoglobin ≥100 g/L.
• Liver/kidney function:
• Albumin ≥3.0 g/dL.
• Total bilirubin <1.5 × ULN.
• ALT/AST <1.5 × ULN.
• Alkaline phosphatase ≤2.5 × ULN.
• BUN and serum creatinine <1.5 × ULN or creatinine clearance >60 mL/min (Cockcroft-Gault formula).
• Coagulation: PT and APTT ≤1.5 × ULN.
• Cardiac function: LVEF ≥55% by echocardiography (ECHO).
• QT interval: QTcF ≤470 ms.
• Reproductive status:
• Premenopausal women: Negative serum pregnancy test within 14 days before treatment.
• Non-lactating.
• All subjects must use effective barrier contraception during treatment and for 6 months post-treatment.
• Informed consent: Willing to sign informed consent and comply with study procedures.
• 3.2 Exclusion Criteria
• Subjects meeting any of the following criteria will be excluded:
• Unconfirmed diagnosis: Breast cancer not histopathologically confirmed.
• Specific subtypes: Bilateral, inflammatory, or occult breast cancer.
• Metastatic disease: Evidence of metastatic breast cancer (excluded via chest/abdominal CT and bone scan; PET/CT allowed as alternative).
• Prior anti-tumor therapy:
• Chemotherapy, radiotherapy, targeted therapy, or endocrine therapy for breast cancer.
• Curative radiotherapy within 4 weeks or palliative radiotherapy within 2 weeks before first dose.
• Prior immunotherapy: Anti-PD-1, anti-PD-L1, anti-PD-L2, or other immune checkpoint inhibitors.
• Concurrent anti-tumor therapy: Any other anti-cancer treatments during the study.
• Second primary malignancy: Except adequately treated non-melanoma skin cancer.
• Transplant history: Prior organ or bone marrow transplantation.
• Recent clinical trials: Participation in another drug trial within 4 weeks prior to enrollment.
• Immunosuppressive therapy: Systemic corticosteroids (>10 mg/day prednisone equivalent) or immunosuppressants within 2 weeks before first dose (excluding inhaled/topical steroids).
• Vaccination: Live or attenuated vaccines within 4 weeks before first dose.
• Major surgery: Non-breast-related major surgery within 4 weeks before first dose or incomplete recovery.
• Autoimmune diseases:
• Active autoimmune disease or history of autoimmune disease with potential recurrence (e.g., autoimmune hepatitis, uveitis, thyroid dysfunction requiring systemic treatment).
• Exceptions: Vitiligo, psoriasis, alopecia, controlled childhood asthma, or type 1 diabetes managed with insulin.
• Immunodeficiency: HIV-positive, congenital/acquired immunodeficiency disorders.
• Cardiovascular disease:
• History within 6 months: Myocardial infarction, stroke (excluding lacunar infarct), pulmonary embolism, unstable angina, NYHA Class III/IV heart failure.
• Clinically significant arrhythmia, primary cardiomyopathy, atrial fibrillation (EHRA ≥2b), uncontrolled hypertension, or QTcF >470 ms.
• Pulmonary disease:
• Interstitial lung disease, idiopathic pulmonary fibrosis, severe COPD/asthma, or autoimmune/collagen vascular diseases with pulmonary involvement.
• Infections:
• Active hepatitis B (HBsAg+ with HBV DNA ≥500 IU/mL), hepatitis C (HCV RNA > ULN), cirrhosis, or severe infections requiring antimicrobial therapy.
• Bleeding/thrombosis disorders: Hereditary/acquired bleeding or thrombotic tendencies (e.g., hemophilia).
• Hypersensitivity: Allergy or contraindication to study drug components.
• Pregnancy/lactation: Pregnant, breastfeeding, or unwilling to use contraception.
• Comorbidities: Uncontrolled conditions (e.g., hypertension, diabetes, active infections) contraindicating ADC or PD-L1 inhibitors.
• Neurological/psychiatric disorders: Epilepsy, dementia, or other conditions deemed unsuitable by the investigator.