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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Sun Yat-sen University
- Enrollment
- 11
- Locations
- 1
- Primary Endpoint
- Safety by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
- Last Updated
- 5 years ago
Overview
Brief Summary
This study is a clinical study on the safety, efficacy and I phase of single center, single arm, open-dose climbing, 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).
Detailed Description
In this study, the dose(number of cells by body weight) and time of infusion should be recorded in detail according to the dosage of slope climbing and single infusion. The safety of chimeric antigen receptor T(CAR-T) cells treatment was evaluated by observing the adverse events after cell therapy. The effectiveness of CAR-T treatment was initially assessed compared with the results of the patient's own previous standard treatment plan. Blood was collected before and within 12 months after infusion to detect the number and activity of CAR-T cells and evaluate the pharmacokinetic characteristics of CAR-T cells.
Investigators
Li Zhang, MD
Professor, Medical doctor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •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;
- •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.
- •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%;
Exclusion Criteria
- •Patients who have previously received any gene therapy product treatment, including CAR-T treatment;
- •Patients with uncontrolled hypertension (\> 160/95), unstable coronary artery disease confirmed by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure(\>New York Heart Association Class II) or myocardial infarction within 6 months before cell infusion;
- •Patients with severe liver and kidney dysfunction or consciousness disorders;
- •Patients who had undergone chemotherapy other than lymphocyte clearance chemotherapy within 14 days before the EGFR CAR-T infusion;
- •Screening of patients who had received other research drugs within 30 days before;
- •Patients undergoing radiotherapy within 2 weeks before infusion;
- •Patients with active hepatitis B: HBVDNA \>1000 cps/ml;
- •Patients with HIV antibody, hepatitis C antibody, syphilis spirocyte positive；
- •Patients with The sputum smear and tuberculosis infection T cell test positive;
- •Patients with Interstitial lung disease or pneumonia;
Outcomes
Primary Outcomes
Safety by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time Frame: In CAR-T cells infusion, up to 52 weeks.
The type, frequency, severity, and duration of adverse events as a result of EGFR CAR T cells infusion will be summarized.
Objective Response Rate (ORR)
Time Frame: In CAR-T cells infusion, up to 52 weeks.
Per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) assessed by MRI or CT. ORR is the percentage of patients at Complete Response (CR) or Partial Response (PR) (according to independent review), prior to progression or further anti-cancer therapy.
Secondary Outcomes
- Peak plasma time (Tmax) of CAR T cells in patients.(In CAR-T cells infusion, up to 6 weeks.)
- Area under the plasma concentration versus time curve (AUC) of CAR T cells in patients.(In CAR-T cells infusion, up to 6 weeks.)
- Peak Plasma Concentration (Cmax) of CAR T cells in patients.(In CAR-T cells infusion, up to 6 weeks.)