CAR T Cell Immunotherapy for Pancreatic Cancer

* Inclusion Criteria

  1. Patients with the following diagnoses:

     1. Cohorts 1 and -1: Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma
     2. Cohort 2: Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma; and either cytologically-proven ascites or known peritoneal disease on radiologic imaging.
     3. Cohort 3 - 4: Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma with liver metastases as confirmed by pathology or radiographic imaging.
  2. INCLUSION CRITERIA HAS BEEN RETIRED
  3. Prior treatment requirements:

     1. Cohorts 1 - 3: Failure of at least one prior standard of care chemotherapy for advanced stage disease.
     2. Cohort 4: At lease stable disease on the first-line standard of care chemotherapy for advanced stage disease.
  4. Cohorts 1-3 and -1: Subjects must have measurable disease as defined by RECIST 1.1 criteria.
  5. Patients ≥ 18 years of age.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  7. Satisfactory organ and bone marrow function as defined by the following:

     i. Absolute neutrophil count ≥ 1,000/μl ii. Platelets ≥75,000/μl iii. Hemoglobin ≥ 8 g/dL iv. Direct bilirubin ≤ 2.0 mg/dl unless the subject has Gilbert's disease syndrome (≤ 3.0 mg.dl) v. Creatinine ≤ 1.5x the institutional normal upper limit vi. Albumin ≥ 2 vii. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5x the institutional normal upper limit viii. Cardiac ejection fraction of ≥40% as measured by resting echocardiogram, with no clinically significant pericardial effusion.
  8. Blood coagulation parameters: PT such that international normalized ratio (INR) is ≤ 1.5 and a PTT ≤ 1.2 time the upper limit of normal unless the patient is therapeutically anti-coagulated for history of cancer-related thrombosis and has stable coagulation parameters.
  9. Provides written informed consent.
  10. Subjects of reproductive potential must agree to use acceptable birth control methods
* Exclusion Criteria:

  1. EXCLUSION CRITERIA HAS BEEN RETIRED
  2. Active invasive cancer other than pancreatic adenocarcinoma. Patients with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder cancer, or prostate cancer with PSA level \< 1.0) are not excluded.
  3. HIV infection
  4. Active hepatitis B or hepatitis C infection
  5. Active autoimmune disease (including but not limited to: systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc.) requiring immunosuppressive therapy within 4 weeks prior to eligibility confirmation by physician-investigator, with the exception of thyroid replacement.
  6. Patients with ongoing or active infection.
  7. Dependence on systemic steroids or immunosuppressant medications.
  8. Patients requiring supplemental oxygen therapy.
  9. Prior therapy with lentiviral gene modified cells.
  10. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
  11. 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.
  12. Any clinically significant pleural or peritoneal effusion that cannot be drained with standard approaches. An indwelling drainage device placed prior to eligibility confirmation by physician-investigator is acceptable.
  13. Pregnant or breastfeeding women.
  14. EXCLUSION CRITERIA HAS BEEN RETIRED
  15. EXCLUSION CRITERIA HAS BEEN RETIRED
  16. Patients with significant lung disease as follows:

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  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. Note: "Greater than lobar" = "in more than 1 lobe".
  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)
  4. Patients with radiographic evidence of significant pleural effusion that is not readily amenable to minimally invasive drainage.

  17\. Cohort 3 and 4 Subjects Only: Patients with a contraindication to IV contrast.