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

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.