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

Trial ID: NCT04146298

Interventional - Phase 1/2 - Recruiting

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.

Conditions

• Pancreatic Cancer
• Pancreatic Neoplasms
• Pancreatic Ductal Adenocarcinoma
• Advanced Cancer

Interventions

• Cyclophosphamide
• Fludarabine
• Mutant KRAS G12V-specific TCR transduced autologous T cells
• Anti-PD-1 monoclonal antibody

Eligibility

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 75 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 100,000/mm\^3.
• Hemoglobin \> 8.0 g/dL.
• Baseline chemistry criteria:
• Serum ALT/AST less than or equal to 3.0 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.
• Serum creatinine less than or equal to 1.6 mg/dL.
• Anticipated lifespan greater than 12 weeks.
• 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.

Sponsor

Changhai Hospital

Source: ClinicalTrials.gov

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