An Exploratory Study to Evaluate the Safety and Preliminary Efficacy of KRAS-Specific Autologous TCR-T Cells in Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- KRAS-specific Autologous TCR-T cell injection
- Conditions
- Colorectal
- Sponsor
- Corregene Biotechnology Co., Ltd
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs)
- Status
- Active, not recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
This is a single-center, open-label, single-arm, dose-escalation study aimed at evaluating the safety and preliminary efficacy of KRAS-specific autologous TCR-T cells in patients with advanced solid tumors harboring KRAS G12V mutation.
Detailed Description
T cell receptor-gene engineered T cells (TCR-T) therapy is a highly targeted form of cellular immunotherapy. It is safer than Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) and is currently a hot topic in immunotherapy. In the case of advanced pancreatic cancer with KRAS mutations, the infusion of TCR-T cells has achieved good efficacy and safety, further suggesting the promising prospects of TCR-T cell immunotherapy for advanced solid tumors with KRAS G12V mutation. It is planned to enroll 9 - 18 patients with advanced solid tumors who have KRAS G12V mutation and HLA-A\*11:01 genotype, and have failed standard treatments. A single-center, open-label, single-arm study design will be adopted. The KRAS-specific autologous TCR-T cell injection will be used to treat these patients. The primary endpoint is safety, and the secondary endpoints include efficacy, cell activity, etc. It is planned to select three dose groups with 5×10⁹, 1×10¹⁰, and 2×10¹⁰ TCR-T cells respectively, and conduct dose escalation using a 3 + 3 study design. The key steps involved in the study are the preparation and quality control of TCR-T cells, lymphocyte depletion (lymphodepletion), and the infusion of autologous TCR-T cell injection. Record and promptly handle specific adverse reactions of cellular immunotherapy, such as cytokine release syndrome (CRS), various other adverse events, off-target effects of TCR-T, and adverse events related to tumorigenic potential, etc., to obtain safety data. It is hoped that the results of this study will bring a new future for patients with advanced solid tumors with specific KRAS mutations.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients aged 18-70 years.
- •Histologically or cytologically confirmed advanced solid tumors (e.g., colorectal cancer, pancreatic cancer, NSCLC) with KRAS G12V mutations and HLA-A\*11:01 genotype.
- •Failed standard therapies or no effective treatment available.
- •ECOG performance status of 0-
- •Life expectancy of ≥3 months.
- •Presence of at least one measurable lesion as defined by RECIST 1.1 criteria.
- •Female patients of childbearing potential must agree to use highly effective contraceptive methods during the study and for at least 6 months after the last dose. A negative pregnancy test within 7 days prior to treatment initiation is required.
- •Written informed consent provided by the patient, with an expectation of compliance with study procedures.
Exclusion Criteria
- •1.Prior treatment with gene-modified T-cell therapies.
- •Current treatment with T-cell suppressive agents (e.g., cyclophosphamide, FK506, tripterygium glycosides) or T-cell stimulants.
- •Chemotherapy, targeted therapy, immunotherapy, or investigational drugs administered within 2 weeks, or radiotherapy within 4 weeks prior to enrollment.
- •Significant organ dysfunction, as evidenced by:
- •leukocytes\<3.0 x 109/L
- •absolute neutrophil count \>1.5 x 109/L
- •hemoglobin\<90g/L
- •platelets \<100 x 109/L
- •Creatinine\>1.5×ULN or creatinine clearance \<50mL/min
- •lymphocytes\<0.5 x 109/L
Arms & Interventions
KRAS-specific Autologous TCR-T cell injection
KRAS-specific Autologous TCR-T cell injection (5×10⁹, 1×10¹°, or 2×10¹° TCR-T cells per dose) with preconditioning lymphodepletion using Fludarabine and Cyclophosphamide, followed by IL-2 support
Intervention: KRAS-specific Autologous TCR-T cell injection
Outcomes
Primary Outcomes
Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs)
Time Frame: 2 years
Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs)
Secondary Outcomes
- Duration of Response (DOR)(2 years)
- Objective Response Rate (ORR)(2 years)
- Disease Control Rate (DCR)(2 years)
- Progression-Free Survival (PFS)(2 years)
- Overall Survival (OS)(2 years)