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Pre-conditioning: Non-myeloablative, lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine

TCR transduced T cell infusion: mutant KRAS G12V-specific TCR transduced autologous T cells (1e9\~1e11). If the participant responds to the first infusion, the second or more infusions will be considered when the disease is progressing.

Anti-PD-1 therapy: anti-PD-1 will be administered if needed.

Cyclophosphamide will be administered prior to cell infusion.

Fludarabine will be administered prior to cell infusion.

After preconditioning regimen, T cells will be infused to the patient intravenously in the Patient Care Unit over approximately 30 to 50 minutes.

Mutant KRAS G12V-specific TCR transduced autologous T cells

During the treatment, anti-PD-1 monoclonal antibody will be administered if needed.

Anti-PD-1 monoclonal antibody

Shiwei Guo, Doctor

Gang Jin, Doctor

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.

Hotspot KRAS mutations exist in various cancers, especially pancreatic, lung and colorectal cancer. Mutations in KRAS are implicated in the development of pancreatic cancer and are associated with poor prognosis of the patients. KRAS is an attractive target for cancer treatment because it is a driver mutation and is likely expressed by all cells in a tumor. Recently,T cells targeting mutant KRAS have been identified in patients with epithelial cancers, and these T-cell receptors (TCR) have been characterized. 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. 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). 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. The investigators will also measure the in vivo survival of engineered T cells.

Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer

Clinical Trial Evaluating the Safety and Activity of Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer

Aggregate of all adverse events, as well as their frequency and severity

Percentage of patients who have a clinical response to treatment (objective tumor regression)

The percentage of TCR transduced T cells in peripheral blood will be detected with an established flow cytometric assay.

The time between cell infusion and the death of patients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer	NCT04146298	Pancreatic Canc... Pancreatic Neop... Pancreatic Duct... Advanced Cancer	Cyclophosphamid... Fludarabine Mutant KRAS G12... Anti-PD-1 monoc...	18 Years - 75 Years	Changhai Hospital
Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer	NCT04146298	Pancreatic Canc... Pancreatic Neop... Pancreatic Duct... Advanced Cancer	Cyclophosphamid... Fludarabine Mutant KRAS G12... Anti-PD-1 monoc...	18 Years - 75 Years	Changhai Hospital

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