This is a single-arm, open-label, one center clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express immune checkpoint antibodies (CTLA-4 and PD-1) and chimeric antigen receptor targeting epidermal growth factor receptor (EGFR-CAR) in adult patients with EGFR positive, advanced recurrent or refractory malignant solid tumors.
This study will be conducted using a phase I/II trial design to assess the efficacy and safety of the CTLA-4 and PD-1 antibodies expressing EGFR-CAR-T for patients with EGFR positive advanced recurrent or refractory malignant solid tumors. EGFR-CAR-T can specificly and effectively kill the EGFR positive cancer cells, CTLA-4 and PD-1 antibodies are secreted from the CAR-T cells could improve immunosuppression microenvironment, new CAR-T cells contain the advantages of CAR-T and immune checkpoint inhibitor, which is a promising therapeutic method for advanced solid tumors. The new CAR-T therapy is applied to clinical practice as bellow. T cells are prepared from peripheral blood mononuclear cells (PBMC) by leukapheresis, then activated and engineered to express CTLA-4 and PD-1 antibodies and chimeric antigen receptor targeting EGFR. Cells are proliferated in culture and returned to the patients by venous transfusion therapy. A total of 40 patients may be enrolled in the study. The total duration of the study is expected to be approximately 24 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Every cycle, peripheral blood mononuclear cells (PBMC) are collected on day 0, CAR-T cells are cultured in a GMP standard workshop. Patients are given a three-day regimen of chemotherapy consisting of cyclophosphamide aimed to deplete the lymphocytes before cells infusion. Then the patients will receive an i.v.gtt infusion of CTLA-4 and PD-1 antibodies expressing EGFR-CAR-T cells at (2-5) ×10\^7 cells/kg from day 18 to day 19 (±2 days). 2 cycles are regarded as a treatment period.
Ningbo No.5 Hospital (Ningbo Cancer Hospital)
Ningbo, Zhejiang, China
RECRUITINGIncidence of treatment-related adverse events as assessed by CTCAE v4.0
Determine treatment-related adverse events of the immunotherapy with common toxicity criteria for adverse effects (CTCAE) version 4.0.
Time frame: 2 years
The response evaluation of of the treatment for advanced solid tumors
The efficacy of the treatment is assessed according to the response evaluation criteria in solid tumor version 1.1 (RECIST1.1), which is defined as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).
Time frame: 2 years
Progression free survival
Progression free survival is defined as the time from the day in which the patient is enrolled to the date on which tumor progresses or the date on which the patient dies for any cause.
Time frame: 2 years
Overall survival
Overall survival is defined as the time from the day in which the patient is enrolled to the date on which the patient dies for any cause.
Time frame: 2 years
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