Efficacy and Safety of Autologous Tumor-Infiltrating Lymphocytes (TIL) Therapy Combined With Pembrolizumab (Keytruda) Immunotherapy in Patients With Advanced or Metastatic Refractory Breast Cancer
This Phase I/II study evaluates the safety and efficacy of autologous tumor-infiltrating lymphocytes (TIL) therapy combined with Pembrolizumab (Keytruda) immunotherapy in patients with advanced or metastatic refractory breast cancer. TILs will be harvested from patients' tumors, expanded in vitro, and infused back into the patients following a non-myeloablative lymphodepletion regimen. Pembrolizumab, a monoclonal antibody that targets the PD-1 receptor on T cells, will be administered to enhance the immune response. The primary endpoint is to determine the objective response rate (ORR) of this combined therapy. Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and quality of life (QoL). This trial aims to provide a novel, personalized treatment option for patients with limited therapeutic alternatives.
• Age: 16 years to 90 years
• Histologically diagnosed as primary/relapsed/metastasized Breast Cancer
• Expected life span more than 3 months
• Karnofsky≥60% or ECOG score 0-2
• Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.
• Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated
• At least 1 evaluable tumor lesion
• Hematology and Chemistry（within 7 days prior to enrollment）:
• Absolute count of white blood cells≥2.5×10\^9/L
• Absolute count of neutropils≥1.5×10\^9/L
• Absolute count of lymphocytes ≥0.7×109/L
• Platelet count≥100×10\^9
• hemoglobin≥90 g/L
• Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days)
• International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days)
• Serum creatinine ≤1.5mg/dL(or ≤132.6μmol/L), or clearance rate≥50mL/min
• Serum ALT/AST ≤3×ULN(subjects with liver metastasis ≤3×ULN)
• Totol bilirubin≤1.5×ULN
• No absolute or relative contraindications to operation or biopsy
• Test subjects with child-bearing potential must be willing to practice approved highly effective methods of contraception at the time of informed consent and continue within 1 year after the completion of lymphodepletion
• Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy, and biologics must cease 28 days before obtaining TILs
• Be able to understand and sign the informed consent document;
• Be able to stick to follow-up visit plan and other requirements in the agreement.