Human Chimeric Antigen Receptor Modified T Cells (huCART-meso) in Combination with VCN-01 for the Treatment of Unresectable or Metastatic Pancreatic or Persistent or Recurrent Ovarian Cancer

Inclusion Criteria

• Patients with one of the following diagnoses: * Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma; OR * Persistent or recurrent serous epithelial ovarian cancer
• Progression or intolerance to at least one prior standard of care chemotherapy for advanced stage disease
• Subjects must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Patients >= 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Hemoglobin >= 9 g/dL
• Platelets >= 75,000/ul
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 x upper limit of normal (ULN)
• Bilirubin =< 2.0 x ULN
• Creatinine =< 1.5 x ULN
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 5 x ULN (subjects with liver metastases) or ALT/AST =< 2.5 x ULN (subjects without liver metastases)
• Must have a minimum level of pulmonary reserve defined as =< grade 1 dyspnea and pulse oxygen > 92% on room air
• Left ventricle ejection fraction (LVEF) >= 40% confirmed by ECHO/multigated acquisition (MUGA)
• Provides written informed consent
• Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria

• Patients with known central nervous system (CNS) metastases
• Active invasive cancer other than the one of the two cancers targeted by this study. Patients with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder and prostate cancer with prostate specific antigen [PSA] level < 1.0) are not excluded
• Active hepatitis B or hepatitis C infection
• Chronic hepatitis C with a FibroScan score equivalent to fibrosis stage 2 (F2) or greater
• Patients with known cirrhosis
• Patients with ongoing or active infection
• Patients with a known history of Li Fraumeni syndrome or retinoblastoma protein pathway germinal deficiency
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to >= 10 mg of prednisone. Patients with autoimmune neurologic diseases (such as multiple sclerosis [MS]) will be excluded
• Planned concurrent treatment with systemic high dose corticosteroids. Patients may be on a stable low dose of steroids (=< 10 mg equivalent of prednisone). Use of inhaled steroids is allowable
• Patients requiring supplemental oxygen therapy
• History of allergy or hypersensitivity to study product excipients (human serum albumin, dimethyl sulfoxide [DMSO], and Dextran 40)
• Any clinically significant pericardial effusion, Class II-IV cardiovascular disability according to the New York Heart Association Classification or other cardiovascular condition that would preclude assessment of mesothelin induced pericarditis or that may worsen as a result of toxicities expected for this study. This determination will be made by a cardiologist if cardiac issues are suspected
• Pregnant or breastfeeding women
• Treatment with a PD-1 or PD-L1 inhibitor, including but not limited to nivolumab, pembrolizumab, atezolizumab, and/or durvalumab, within 2 months prior to eligibility confirmation by a physician-investigator
• Patients with significant lung disease as follows: * Patients with radiographic evidence of greater than lobar lymphangitic pulmonary involvement, greater than lobar bronchial wall thickening suggestive of peribronchial lymphatic disease extension, and/or evidence of extensive bilateral parenchymal metastatic burden * Patients with radiographic and/or clinical evidence of active radiation pneumonitis * Patients with radiographic evidence of underlying interstitial lung disease, including evidence of unresolved drug toxicity from any agent (e.g. chemotherapy, targeted agents, amiodarone, nitrofurantoin, etc.)