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

• Status: Recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Changhai Hospital; Guo ShiWei
• Collaborator: Providence Cancer Center, Earle A. Chiles Research Institute
• Treatments: Antibodies; Antibodies, Monoclonal; Cyclophosphamide; Fludarabine; Fludarabine phosphate

Criteria

Inclusion Criteria:

• Patients with measurable and pathologically confirmed advanced pancreatic cancer, including metastatic pancreatic cancer (who have received standard chemotherapy) and recurrent pancreatic cancer (who have received surgery and adjuvant chemotherapy previously).

• 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.

• Patients must be HLA-A*11:01.

• Patients with brain metastasis may be eligible if they are asymptomatic and there are fewer than 3 brain lesions that are each less than 1 cm in diameter.

• Patients between 18 to 70 years old are eligible.

• Patients should have good clinical performance status (ECOG 0 or 1).

• Patients must practice birth control once enrolled into the study and for up to four months after therapy.

• Patients must be seronegative for HIV antibody.

• Patients must be seronegative for hepatitis B surface antigen and core antibody (or HBV non-detectable by QPCR).

• Patients must be seronegative for hepatitis C antibody (or HCV non-detectable by QPCR).

• Baseline hematology criteria:

• Absolute neutrophil count of at least 1000/mm^3.

• White blood cell count of at least 3000/mm^3.

• Platelet count of at least 75,000/mm^3.

• Hemoglobin > 8.0 g/dL.

• Baseline chemistry criteria:

• Serum ALT/AST less than or equal to 5.0 x ULN.

• Total bilirubin less than or equal to 1.5 mg/dL, unless the patient has Gilbert's Syndrome in which case total bilirubin must be less than or equal to 3.0 mg/dL.

• eGFR> 60 mL/m or a formal 6-24h CrCl> 60 mL/m.

• Patients must be willing and able to comply with all study-related procedures and follow-up requirements.

• Patients must be able to understand and sign a written Informed Consent Document as well as a durable power of attorney.

Exclusion Criteria:

• Women who are pregnant or breastfeeding.

• Patients with any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease or HIV).

• Patients with active systemic infections, coagulation disorders, or any other major medical illnesses.

• Patients with concurrent opportunistic infections.

• Patients on concurrent systemic steroid therapy.

• Patients with a history of severe immediate hypersensitivity reaction to any of the medicines used in this study (e.g., cyclophosphamide, fludarabine).

• Patients with active coronary ischemic symptoms.

• Patients who are receiving any other investigational agents.