The Clinical Study of the Efficacy and Safety of Trop2-ADC Monotherapy or Combination Immunotherapy Strategy in the Treatment of Advanced Triple-negative Breast Cancer.

Randomized Controlled Clinical Study of Efficacy and Safety of Trop2-ADC Monotherapy or Combination Immunotherapy Strategies in the Treatment of Advanced Triple-negative Breast Cancer

This is a prospective, multicenter, randomized controlled study aimed at evaluating the efficacy and safety of Trop2-ADC monotherapy or immune combination strategy in the treatment of advanced triple-negative breast cancer.

This prospective, multicenter, randomized controlled study aims to evaluate the 3-month treatment efficacy (ORR) of three therapeutic strategies-ADC monotherapy, ADC in combination with immunotherapy, and ADC in combination with immunotherapy and anti-angiogenesis-in patients with advanced breast cancer, and to assess potential adverse events related to the treatment regimens. Participants will receive treatment with a Trop-2-targeting ADC drug containing a TOP1 inhibitor (such as Gosituzumab or SKB264), in accordance with the defined protocol. Regular assessments will include imaging, histopathological analysis, and safety monitoring. The objective of this study is to provide novel treatment strategies for triple-negative breast cancer by evaluating the efficacy and safety of trop2-ADC+ immunotherapy + antiangiogenic agents and trop2-ADC+ antiangiogenic agents versus trop2-ADC monotherapy in patients with metastatic triple-negative breast cancer (mTNBC).

Inclusion Criteria:

• 1) adult female patients (aged 18-70 years) with metastatic triple negative breast cancer confirmed by pathology or imaging;
• 2) no more than two previous lines of therapy for metastatic disease;
• 3) ECOG performance status ≤2 and expected survival time ≥ 3 months;
• 4) At least one measurable lesion on imaging within 2 weeks before enrollment; Or simple bone metastases;
• 5) Prior treatment-related toxicity at enrollment had to be resolved to NCI CTCAE version 5.0 ≤ grade 1 (excluding alopecia or any other toxicity deemed by the investigator to be of no risk to patient safety)
• 6) adequate bone marrow reserve: a. White blood cell count (WBC) ≥3.0×10^9 / L, b. Neutrophil count (ANC) ≥1.5×10^9 / L, c. Platelet count (PLT) ≥70×10^9 / L
• 7) liver, kidney and heart function tests were basically normal (according to the normal values of the laboratories in the study center) : a. Total bilirubin (TBIL) ≤3× upper limit of normal value (ULN), b. alanine aminotransferase and aspartate aminotransferase (ALT/AST) ≤2.5×ULN (≤5xULN in patients with liver metastases), c. Total bilirubin (TBIL) ≤3× upper limit of normal value (ULN), B. alanine aminotransferase and aspartate aminotransferase (Alt /AST) ≤2.5×ULN (≤5xULN in patients with liver metastases). Serum creatinine ≤1.5×ULN or creatinine clearance (Ccr) ≥60 ml/min; d. Left ventricular ejection fraction (LVEF) ≥ 55%, e. QTcF(Fridericia correction) ≤ 470 ms.
• 8) understood the study process and volunteered to participate in the study. Informed consent was signed.

Exclusion Criteria:

• 1) patients with a known allergy to the active ingredient or other ingredient of the study drug.
• 2) patients with known resistance to trop2-ADC drugs. 、
• 3) receiving radiotherapy, chemotherapy, or endocrine therapy within 4 weeks before enrollment, or participating in any interventional drug clinical trial;
• 4) pregnant or lactating women or women of childbearing age who refused to use effective contraception during the study period.
• 5) patients with severe cardiac disease or discomfort expected to be unable to tolerate chemotherapy, including but not limited to: fatal arrhythmia or higher grade atrioventricular block, unstable angina pectoris, clinically significant valvular heart disease, transmural myocardial infarction on ECG, uncontrolled hypertension;
• 6) any other condition considered by the investigator to be inappropriate for participation in the study, a concomitant disease or condition that could interfere with participation in the study, or any serious medical disorder that could affect the safety of the subject (e.g., uncontrolled heart disease, hypertension, active or uncontrolled infection, active hepatitis B virus infection)；