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

This is an interventional treatment trial for Pancreatic Cancer Read More

Inclusion Criteria:

1. Patients with one of the following diagnoses:

   1. Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma; OR
   2. Persistent or recurrent serous epithelial ovarian cancer
2. Progression or intolerance to at least one prior standard of care chemotherapy for advanced stage disease.
3. Subjects must have measurable disease as defined by RECIST 1.1 criteria.
4. Patients ≥ 18 years of age.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Adequate organ and bone marrow function defined as:

   1. Hemoglobin ≥ 9 g/dL
   2. Platelets ≥ 75,000/µl
   3. PT/INR and PTT ≤ 1.5 x ULN
   4. Bilirubin ≤ 2.0 x ULN
   5. Creatinine ≤ 1.5 x ULN
   6. ALT/AST ≤ 5 x ULN (subjects with liver metastases) or ALT/AST ≤ 2.5 x ULN (subjects without liver metastases)
   7. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air
   8. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
7. Provides written informed consent.
8. Subjects of reproductive potential must agree to use acceptable birth control methods, 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 not excluded.
3. Active hepatitis B or hepatitis C infection.
4. Chronic hepatitis C with a FibroScan score equivalent to fibrosis stage 2 (F2) or greater.
5. Patients with known cirrhosis.
6. Patients with ongoing or active infection.
7. Patients with a known history of Li Fraumeni syndrome or retinoblastoma protein pathway germinal deficiency.
8. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 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 may be on a stable low dose of steroids (≤ 10mg equivalent of prednisone). Use of inhaled steroids is allowable.
10. Patients requiring supplemental oxygen therapy.
11. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
12. Any clinically significant pericardial effusion, Class II-IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 4) 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.
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 eligibility confirmation by a physician-investigator.

15. Patients with significant lung disease as follows:

    1. 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.
    2. Patients with radiographic and/or clinical evidence of active radiation pneumonitis.
    3. 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.)