Pilot Study of Autologous T-cells in Patients With Metastatic Pancreatic Cancer

Pilot Study of Autologous T-cells Redirected to Mesothelin and CD19 With a Chimeric Antigen Receptor in Patients With Metastatic Pancreatic Cancer

This is a study in which pancreatic cancer patients receive a combination therapy with CART-meso cells and CART19 cells administered at 3 days after one dose of cyclophosphamide. CART-meso cells are patients' own T cells that were modified in the laboratory to express a receptor specific to the mesothelin protein. CART19 cells are patients' own T cells that were modified in the laboratory to express a receptor specific to a protein called CD19. The CD19 protein is expressed on white blood B cells. CART19 cells are expected to attack the B cells and impede the antibody response against CART-meso cells. The investigators hypothesize that this combination therapy may prolong the duration of CART-meso cells in the body. Additionally, one dose of cyclophosphamide may enhance engraftment and persistence of CART cells.

Immunotherapy is a novel and promising approach for the treatment of solid tumors; immunotherapy with chimeric antigen receptor (CAR) T cells (CART cells) in particular has the potential advantage of targeted therapies that can invoke a rapid tumor response, and the advantage of long-lived responses that are the hallmark of engagement of the adaptive immune system such as memory T cells.

This is a single arm, open-label, phase I study to determine the safety and feasibility of combination CART-meso cells (autologous T cells lentivirally transduced to express anti-mesothelin scFv fused to TCRζ and 4-1BB costimulatory domains) and CART19 cells (autologous T cells lentivirally transduced to express a humanized anti-CD19 scFv fused to TCRζ and 4-1BB costimulatory domains) in patients with pancreatic cancer following lymphodepletion with cyclophosphamide.

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 years of age and older
• 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
• History of allergy to murine proteins
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
• Clinically significant pericardial effusion, CHF, or cardiovascular condition that would preclude assessment of mesothelin induced pericarditis or that may worsen as a result of toxicities expected for this study
• Pregnant or breastfeeding women