Adaptive Chemotherapy for the Treatment of Advanced Breast Cancer

A Prospective, Multicenter Phase Ⅲ Clinical Trial of Adaptive Chemotherapy for Advanced Breast Cancer After Standard Treatment

The primary objective of this study is to explore the efficacy and safety of adaptive therapy in the treatment of advanced breast cancer progressive after standard treatment.

This is a prospective, multicenter phase Ⅲ clinical Trial. The objective of the study is to evaluate the efficacy and safety of adaptive chemotherapy vs. conventional chemotherapy in the treatment of advanced breast cancer progressive after standard treatment. The therapy regimen, primarily including gemcitabine, vinorelbine, or eribulin, will be selected by the investigator based on current guidelines, available treatments, and an assessment of the patient's clinical status, preferences, and financial situation. This study is designed to recruit up to 192 subjects.

Inclusion Criteria:

• Understands and voluntarily signs the informed consent form.
• ECOG PS of 0 or 1.
• Expected survival: >3 months
• Histologically or cytologically confirmed advanced invasive breast cancer.
• Histological type: HR+/HER2- or HR-/HER2-. HR positivity is defined as ER and/or PR expression in ≥1% of tumor cells by IHC. HER2 negativity is defined according to the ASCO-CAP HER2 guidelines: IHC intensity of 0 or 1+, or IHC intensity of 2+ with negative in situ hybridization results.
• Previous failure of first-line treatment for metastatic disease. For HR+/HER2- patients: at least received endocrine therapy combined with CDK4/6 inhibitors. TNBC patients at least received chemotherapy combined with PD-1 inhibitors (if PD-L1 CPS ≥1), or PARP inhibitor treatment (if germline BRCA mutations), except for TNBC patients with known germline BRCA mutations whom the attending physician deems them unable or unsuitable for PARP inhibitor treatment.
• At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• Adequate organ function including bone marrow, renal function, hepatic function, and cardiac reserve.
• Premenopausal women must use medically acceptable contraception during the study.
• Compliance with the study protocol.

Exclusion Criteria:

• The investigator considers that the presence of the following factors would be unfavorable to the subject's participation in the study or may affect protocol compliance, such as uncontrolled hypertension, persistent or active infection, etc.
• Persistent toxicities caused by previous anti-tumor treatment that have not improved to ≤ Grade 2 or baseline levels.
• Neoplastic spinal cord compression or active brain metastases.
• Significant third-space fluid retention (e.g., ascites or pleural effusion).
• Uncontrolled infection requiring treatment with intravenous antibiotic.
• Active or uncontrolled hepatitis B or hepatitis C virus infection.
• Uncontrolled or significant heart disease.
• Suspected ILD/non-infectious pneumonia.
• Active autoimmune disease or inflammatory disease (including inflammatory bowel disease.