Phase I Study of Specific CAR-T Dual-targeting HER2 and PD-L1 for HER2-positive Solid Tumors
CAR-T therapy has achieved unprecedented success in hematological tumors in recent years, but the progress of CAR-T cells in the treatment of solid tumors is facing difficulties. HER-2 is frequently expressed in breast cancer, ovarian cancer, lung cancer, gastric cancer and other malignant tumors. In this study, the PD-L1 inhibitory signal was transformed into an activation signal in the tumor microenvironment, and enhanced the killing activity and survival ability of CAR-T cells. The HER-2/PD-L1 dual-targeting CAR-T will be investigated in patients with HER2-positive solid tumors, and all enrolled subjects will receive HER2/PD-L1 CAR T cells via intravenous or thoracic/peritoneal cavity infusion.
• Male or female, Age 18-75 years old; If the subjects are over 75 years old, the researchers will determine whether to enroll according to the basic health conditions of the subjects, regardless of gender. No upper age limit was set for chest/abdominal reinfusion CAR-T subjects.
• Estimated life expectancy ≥ 3 months (according to investigator's judgement);
• The Eastern Cooperative Oncology Group (ECOG) performance status score is 0-2;
• Patients diagnosed as ovarian cancer, non-small cell lung cancer, breast cancer, gastric cancer, head and neck cancer, pancreatic cancer, colorectal cancer, transitional cell carcinoma, endometrial carcinoma, sarcoma, glioblastoma, cholangiocarcinoma, etc. have received standard systemic treatment, have systemic metastasis/serosal cavity metastasis or are not tolerated;
• Expressing HER2 \>20% of primary tumors or metastatic cells in the serous cavity by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH);
• Absolute neutrophil count ≥ 1×10\^9/L, platelet count ≥ 75×10\^9/L, absolute lymphocyte count ≥0.5×10\^8/L, hemoglobin ≥ 8.0 g/dl;
• Creatinine clearance rate ≥60ml/min, Serum ALT/AST≤2.5 times of the normal level, and total bilirubin≤1.5 times of the normal level;
• Cardiac ejection fraction ≥50%, no pericardial effusion;
• No other serious diseases (autoimmune diseases or any immune deficiency disease or other disease in need of immunosuppressive therapy);
⁃ Patients must stop chemotherapy and targeted therapy for at least 3 weeks before starting treatment;
⁃ Patients must take reliable contraceptive measures before entering the trial, during the research process until 1 year after CAR-T infusion; reliable contraceptive measures will be determined by the main investigator or designated personnel;
⁃ Voluntarily participate in the research, understand and sign the informed consent;
⁃ The side effect of the last anti-tumor treatment was reduced to ≤1 grade, except for hair loss.