A Clinical Study of CTLA-4 and PD-1 Antibodies Expressing EGFR-CAR-T Cells for Patients With EGFR Positive Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Advanced Solid Tumor
- Sponsor
- Shanghai Cell Therapy Research Institute
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Incidence of treatment-related adverse events as assessed by CTCAE v4.0
- Last Updated
- 8 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with relapsed or refractory advanced solid malignancies (diagnosed by histology or cytology detection).
- •Progressive disease and no response after at least second-line therapy.
- •Gender unlimited, age from 18 years to 80 years.
- •Life expectancy ≥3 months.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Adequate venous access for peripheral blood mononuclear cell (PBMC) apheresis, and no other contraindications.
- •Immunohistochemistry (IHC) score of EGFR on tumor tissue ≥1+.
- •Adequate hepatic function, renal function and bone marrow function (withhin 7 days before enrollment): white blood cell (WBC) ≥3.0×10\^9/L; platelet ≥100×10\^9/L; hemoglobin ≥90 g/L; lymphocyte ≥0.7×10\^9/L; total bilirubin ≤2 times the upper limit of the normal value; alanine aminotransferase and aspartate transaminase(ALT and AST) ≤2.5 times the upper limit of the normal value; serum creatinine ≤1.5 times the upper limit of the normal value.
- •There is no other treatments (chemotherapy, radiotherapy, etc.) within four weeks before enrollment.
- •There is at least one measurable tumor lesion.
Exclusion Criteria
- •Patients with two or more kinds of tumors.
- •Patients with active viral or bacterial infection, and have failed to be controlled by anti-infective treatment.
- •Patients with seropositive reponse of Human immunodeficiency virus (HIV) and syphilis, or fail to control the hepatitis B virus or hepatitis C virus infection.
- •Patients with active rheumatic diseases, organ transplantation and other diseases affecting the immune system seriously.
- •Patients with severe heart and lung dysfunction.
- •Patients with severe chronic diseases of kidney, liver and other important organs.
- •Patients with any other serious illnesse that the investigators consider it will may affect the patient's treatments, follow-up or assessment, including any uncontrolled clinically significant neurological or psychiatric disorders, immunoregulatory diseases, metabolic diseases, infectious diseases and so on.
- •Patients who take part in clinical trials of other drugs or biological therapy at present or within 30 days before enrollment.
- •Patients who need long-term use of immunosuppressive drugs or patients who are undergoing treatment of autoimmune diseases.
- •Patients who need long-term use of glucocorticoid.
Outcomes
Primary Outcomes
Incidence of treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 2 years
Determine treatment-related adverse events of the immunotherapy with common toxicity criteria for adverse effects (CTCAE) version 4.0.
Secondary Outcomes
- The response evaluation of of the treatment for advanced solid tumors(2 years)
- Overall survival(2 years)
- Progression free survival(2 years)