huCART-meso + VCN-01 in Pancreatic and Ovarian Cancer

Inclusion Criteria:

1. Patients with one of the following diagnoses:

2. Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma;OR

3. Persistent or recurrent serous epithelial ovarian cancer

4. Progression or intolerance to at least one prior standard of care chemotherapy foradvanced stage disease.

5. Subjects must have measurable disease as defined by RECIST 1.1 criteria.

6. Patients ≥ 18 years of age.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

8. Adequate organ and bone marrow function defined as:

9. Hemoglobin ≥ 9 g/dL

10. Platelets ≥ 75,000/µl

11. PT/INR and PTT ≤ 1.5 x ULN

12. Bilirubin ≤ 2.0 x ULN

13. Creatinine ≤ 1.5 x ULN

14. ALT/AST ≤ 5 x ULN (subjects with liver metastases) or ALT/AST ≤ 2.5 x ULN (subjects without liver metastases)

15. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea andpulse oxygen > 92% on room air

16. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA

17. Provides written informed consent.

18. Subjects of reproductive potential must agree to use acceptable birth controlmethods, as described in the protocol

Exclusion Criteria:

1. Patients with known CNS metastases

2. 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 PSA level < 1.0) are notexcluded.

3. Active hepatitis B or hepatitis C infection.

4. Chronic hepatitis C with a FibroScan score equivalent to fibrosis stage 2 (F2) orgreater.

5. Patients with known cirrhosis.

6. Patients with ongoing or active infection.

7. Patients with a known history of Li Fraumeni syndrome or retinoblastoma proteinpathway germinal deficiency.

8. Active autoimmune disease requiring systemic immunosuppressive treatment equivalentto ≥ 10 mg of prednisone. Patients with autoimmune neurologic diseases (such as MS)will be excluded.

9. Planned concurrent treatment with systemic high dose corticosteroids. Patients maybe on a stable low dose of steroids (≤ 10mg equivalent of prednisone). Use ofinhaled steroids is allowable.

10. Patients requiring supplemental oxygen therapy.

11. History of allergy or hypersensitivity to study product excipients (human serumalbumin, DMSO, and Dextran 40).

12. Any clinically significant pericardial effusion, Class II-IV cardiovasculardisability according to the New York Heart Association Classification (see Appendix

4. or other cardiovascular condition that would preclude assessment of mesothelininduced pericarditis or that may worsen as a result of toxicities expected for thisstudy. This determination will be made by a cardiologist if cardiac issues aresuspected.

13. Pregnant or breastfeeding women.

14. 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 eligibilityconfirmation by a physician-investigator.

15. Patients with significant lung disease as follows:

16. Patients with radiographic evidence of greater than lobar lymphangiticpulmonary involvement, greater than lobar bronchial wall thickening suggestiveof peribronchial lymphatic disease extension, and/or evidence of extensivebilateral parenchymal metastatic burden.

17. Patients with radiographic and/or clinical evidence of active radiationpneumonitis.

18. 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.)