Refining neoadjuvant chemoimmunotherapy and establishing predictive biomarkers remain pivotal challenges in early TNBC. Although SG/I (sacituzumab govitecan/PD-1 inhibitor) shows clinical promise, validation of responder identification tools is warranted. This phase II trial aims to identify a precision TNBC population suitable for de-escalated neoadjuvant therapy with sacituzumab govitecan plus tislelizumab, based on differential Trop-2 expression (±) and PD-L1 status (CPS \>10% vs. \<10%). Primary endpoints include pCR rate and safety; exploratory biomarker analyses will assess mechanisms of response/resistance
1. Age ≥ 18 years; 2. Histologically confirmed stage II or III primary invasive TNBC TNBC defined as: immunohistochemistry (IHC) ER and PR <1%; HER2-negative, IHC 0 or 1+, IHC 2+, ISH-; 3. ECOG performance status score 0-1; 4. Provision of an acceptable tumor sample prior to randomization; 5. Bone marrow hematopoietic and organ function must meet study requirements; Without growth factor support or blood transfusion, ANC ≥ 1.5 × 10⁹/L, platelets ≥ 100 × 10⁹/L, hemoglobin ≥ 9 g/dL; Bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 2.5 × ULN; Creatinine ≤ 1.5 × ULN; Urinalysis showing proteinuria < 2+ or 24-hour urine protein < 1 g; Coagulation function must be normal, defined as: International Normalized Ratio (INR) and/or Prothrombin Time (PT) ≤ 1.5 × ULN and/or Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN. If anticoagulant therapy is ongoing, PT must remain within the therapeutic range for the anticoagulant used.
1. Evidence of severe/uncontrolled systemic disease, including active infections requiring intravenous therapy, severe chronic gastrointestinal disease associated with diarrhea, active bleeding disorders, severe cardiac or psychiatric disorders, or history of allogeneic organ transplantation; 2. History of other primary malignancies with known active disease within 3 years prior to randomization and low potential for recurrence (excluding adequately excised non-melanoma skin cancers and treated carcinoma in situ); 3. Active or documented history of autoimmune or inflammatory diseases; 4. Presence of distant metastases; 5. Active or uncontrolled hepatitis B or C infection, uncontrolled HIV infection, or active tuberculosis; 6. History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, any clinically active interstitial lung disease, or immune-related pneumonitis induced by immunotherapy; 7. Any prior or concurrent surgery, radiotherapy, or systemic anticancer therapy for TNBC; 8. Prior exposure to the following treatments: Immunosuppressive drug therapy within 14 days before the first study intervention Live attenuated vaccines within 30 days before the first study intervention
First Hospital of China Medical University
Lead sponsor
Liaoning Cancer Hospital & Institute
Collaborator