This clinical trial will evaluate the safety and activity of mutant KRAS G12V-specific TCR transduced T cell therapy for advanced pancreatic cancer patients who express the KRAS G12V mutation and HLA-A*11:01 allele. The theoretical basis of this study is that mutant KRAS antigen-specific TCR transduced autologous Tcells will target and kill HLA-matched mutant KRAS cancer cells but not normal cells.
Name: Cyclophosphamide
Name: Fludarabine
Name: Mutant KRAS G12V-specific TCR transduced autologous T cells
Name: Anti-PD-1 monoclonal antibody
Description: Aggregate of all adverse events, as well as their frequency and severity
Measure: Frequency and severity of treatment-related adverse events Time: 2 years following cell infusionDescription: Percentage of patients who have a clinical response to treatment (objective tumor regression)
Measure: Objective response rate Time: From the date of cell infusion to disease progression (up to 24 months after cell infusion).Description: The percentage of TCR transduced T cells in peripheral blood will be detected with an established flow cytometric assay.
Measure: The percentage of TCR transduced T cells in peripheral blood Time: 2, 6 and 12 weeks after cell infusion, then every 3 months, and up to 24 months after cell infusion.Description: The time between cell infusion and the death of patients
Measure: Overall survival Time: From date of cell infusion until the date of death from any cause, whichever came first, assessed up to 24 months after cell infusion.Allocation: N/A
Single Group Assignment
There are 2 SNPs
For example, TCRs that target mutant KRAS G12D peptides presented by HLA-C*08:02, and a TCR that targets a KRAS G12V peptide presented by HLA-A*11:01 have been identified. --- G12D ---
Mutant KRAS-reactive T cells appear capable of inducing tumor regression as highlighted in a patient with metastatic colorectal cancer who experienced regression of metastatic tumors after infusion of HLA-C*08:02-restricted KRAS-G12D reactive tumor-infiltrating lymphocytes (TIL). --- G12D ---
Clinical Trial Evaluating the Safety and Activity of Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer. --- G12V ---
Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer This clinical trial will evaluate the safety and activity of mutant KRAS G12V-specific TCR transduced T cell therapy for advanced pancreatic cancer patients who express the KRAS G12V mutation and HLA-A*11:01 allele. --- G12V ---
Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer This clinical trial will evaluate the safety and activity of mutant KRAS G12V-specific TCR transduced T cell therapy for advanced pancreatic cancer patients who express the KRAS G12V mutation and HLA-A*11:01 allele. --- G12V --- --- G12V ---
Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer This clinical trial will evaluate the safety and activity of mutant KRAS G12V-specific TCR transduced T cell therapy for advanced pancreatic cancer patients who express the KRAS G12V mutation and HLA-A*11:01 allele. --- G12V --- --- G12V --- --- G12V ---
- Patient's tumor must express the KRAS G12V mutation, or a G12V mutation in HRAS or NRAS, as determined by DNA or RNA sequencing methods. --- G12V ---
- Patient's tumor must express the KRAS G12V mutation, or a G12V mutation in HRAS or NRAS, as determined by DNA or RNA sequencing methods. --- G12V --- --- G12V ---
For example, TCRs that target mutant KRAS G12D peptides presented by HLA-C*08:02, and a TCR that targets a KRAS G12V peptide presented by HLA-A*11:01 have been identified. --- G12D --- --- G12V ---
The investigators will test the safety and activity of adoptive transfer of autologous T cells genetically engineered to express a TCR that targets mutant KRAS G12V in the context of HLA-A*11:01 in HLA-matched patients with advanced pancreatic cancer that express mutant KRAS G12V. --- G12V ---
The investigators will test the safety and activity of adoptive transfer of autologous T cells genetically engineered to express a TCR that targets mutant KRAS G12V in the context of HLA-A*11:01 in HLA-matched patients with advanced pancreatic cancer that express mutant KRAS G12V. --- G12V --- --- G12V ---