A Single-arm, Open-label, Phase I Study to Evaluate the Safety and Efficacy of CXCR5 Modified EGFR Chimeric Antigen Receptor Autologous T Cells in EGFR-positive Patients With Advanced Non-small Cell Lung Cancer
This study is a single arm, open-label, intravenous infusion of Anti- Epidermal growth factor receptor (EGFR) Chimeric Antigen Receptor (CAR) T cells modified by C-X-C Chemokine receptor type 5 (CXCR 5) in patients with advanced adult non-small cell lung cancer (NSCLC).
• All subjects or legal guardians must sign the informed consent form approved by the ethics committee in writing before starting any screening procedure;
• 18 Years to 75 Years, Histologically or cytologically confirmed Routine treatment of patients with advanced non-small cell lung cancer(Including TKI treatment failure patients);
• After the signature of the informed consent and prior to the collection of a single nuclear cell, the immuno- histochemical test must determine that the expression of EGFR in the tumor site of the patient reaches the positive standard and the score is 2 + or more;
• Pathological results suggest that CXCL13 factor positive rate ≥ 10 %;
• According to RECIST 1.1. The patient has at least one tumor lesion that can be measured (Results available within one month prior to screening period);
• Expected survival time ≥ 12 weeks;
• The Eastern oncology group strength status score (ECOG) was 0-1;
• Patients must have evidence of adequate hepatic and renal function as evidenced by the following laboratory parameters: Serum creatinine≤ 1.6 mg/ml or the creatinine clearance ≥ 40 ml/min/1.73m. Total bilirubin \< 1.5 times upper limits of normal;
• The hemodynamics determined by echocardiography or multichannel radionuclide angiography(MUGA) are stable and the left ventricular ejection fraction (LVEF)≥50%;
⁃ Have sufficient bone marrow reserves (subjects can meet this requirement through blood transfusion), defined as: The number of white blood cells should not be less than 2 × 10\^9/L;Platelet≥100 x 10\^9/L; Hemoglobin ≥100 g/L;
⁃ If the patient uses the following drugs, the following conditions must be met:
⁃ Glucocorticoid: The therapeutic dose of glucocorticoid must be stopped 2 weeks before the EGFR CAR-T infusion. However, the following physiological replacement doses of glucocorticoids are allowed: 12 mg/m2 / dihydrogenated cortisone or equivalent; Immunosuppressive drugs: any immunosuppressive drugs must be stopped before they are selected for 4 weeks; Stop using granulocyte colony factor a week before plasmaphoresis.
⁃ Women of childbearing age and all male subjects must agree to use effective contraceptive methods for at least 52 weeks after EGFR CAR-T infusion, and until two consecutive PCR tests show that CAR-T cells are no longer present in the body.