Study of Autologous T-cells Redirected to Mesothelin With a Chimeric Antigen Receptor in Patients With Metastatic Pancreatic Cancer
Overview
- Phase
- Not Applicable
- Sponsor
- Shenzhen BinDeBio Ltd.
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Safety of CART-meso infusion: number of adverse events
Overview
Brief Summary
This is a study in which pancreatic cancer patients receive a immunotherapy with CART-meso cells administered at 3 days after one dose of cyclophosphamide. CART-meso cells are patients' own T cells lentivirally transduced to express anti-mesothelin scFv fused to TCRζ and 4-1BB costimulatory domains.The lymphodepletion with cyclophosphamide may prolong the persistence of CART cells.
Detailed Description
This study is being conducted to assess the safety and efficacy of immunotherapy with CART-meso cells in dose escalation design. The trial will begin in Cohort 1 and progress to Cohorts 2, depending upon dose limiting toxicity (DLT) assessment .
Subjects will be enrolled serially, but infusions will be staggered to allow assessment of DLTs for determination of cohort progression, expansion, or dose de-escalation.
Cohort 1 subjects will receive a single dose of 1-3x10^7 /m^2 lentiviral transduced CART-meso cells after conditioning chemotherapeutic regimen.
Cohort 2 subjects will receive a single dose of 1-3x10^8 /m^2 lentiviral transduced CART-meso cells cells after conditioning chemotherapeutic regimen.
Dose limiting toxicity is defined as any adverse reactions at level 3 or above that may be associated with CART-meso within 4 weeks after infusion.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Signed informed consent
- •Unresectable or metastatic pancreatic cancer
- •Persistent cancer after at least one prior standard of care chemotherapy for advanced stage disease
- •18 - 70 years of age
- •ECOG performance status of 0 or 1
- •Life expectancy greater than 3 months
- •Satisfactory organ and bone marrow function
- •Meets blood coagulation parameters
- •Male and Female subjects of reproductive potential agree to use approved contraceptive methods
Exclusion Criteria
- •Participation in a therapeutic investigational study within 4 weeks prior to the screening visit
- •Anticipated need for systemic chemotherapy within 2 weeks before apheresis and infusion
- •Active invasive cancer other than pancreatic cancer
- •HIV, HCV, or HBV infections
- •Active autoimmune disease requiring immunosuppressive therapy within 4 weeks prior to screening visit, with exception of thyroid replacement
- •Ongoing or active infection
- •Planned concurrent treatment with systemic high dose corticosteroids
- •Patients requiring supplemental oxygen therapy
- •Prior therapy with gene modified cells
- •Previous experimental therapy with SS1 moiety, murine or chimeric antibodies
Outcomes
Primary Outcomes
Safety of CART-meso infusion: number of adverse events
Time Frame: 60 months
Number of Adverse Events evaluated with NCI CTC AE, version 4.0\[Safety evaluation\]
Secondary Outcomes
- Clinical response of CART-meso(60 months)
- CAR-T cell detection(60 months)