Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer
Recruiting · NCT04146298 · Interventional (participants receive a specific treatment) · Lead sponsor: Changhai Hospital
View the official record on ClinicalTrials.gov →Interventions studied
Anti-PD-1 monoclonal antibodyCyclophosphamideFludarabineMutant KRAS G12V-specific TCR transduced autologous T cells
What this trial is about
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.
Who can take part
Age range
18 Years to 75 Years
Sex
All (male and female)
Healthy volunteers
No - a diagnosis or condition is required
Phase
Phase 1, Phase 2
Study type
Interventional (participants receive a specific treatment)
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.
Where it is running
1 location listed.
- Changhai Hospital - Shanghai, China