Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the Cancer-Cell Surface Antigen Mesothelin

Inclusion Criteria

• •Patients with MPD aged ≥18 years
• •Karnofsky performance status ≥70%
• •Patients with malignant pleural disease (MPD), pathologically confirmed at MSKCC (radiographic confirmation is acceptable for screening phase eligibility), and defined as one of the following (patients who have not yet received treatment may enroll in the screening portion only):
• •1. Malignant pleural mesothelioma - previously treated with at least one prior treatment regimen.
• •2. Non-small cell lung cancer metastatic to the pleura-previously treated with at least one prior treatment regimen (chemotherapy or targeted agent) and documented progression of disease. Patients with disease outside of the pleura will be discussed among study PI and Co-PIs prior to considered eligible for the study. Disease outside of the pleura must not require any immediate therapy per PI's discretion.
• •3. Breast cancer metastatic to the pleura- previously treated with at least one prior treatment regimen (chemotherapy or targeted agent) and documented progression of disease. Patients with disease outside of the pleura will be discussed among study PI and Co-PIs prior to be considered eligible for the study. Disease outside of the pleura must not require any immediate therapy per PI's discretion.
• •Only patients with a diagnosis of malignant pleural mesothelioma will be included in cohort 9 and in the Phase II portion of the study
• •Expression of mesothelin must be confirmed by meeting one of the following criteria.
• •1. Mesothelin expression (\>10% of the tumor expressing mesothelin) by immunohistochemical (IHC) analysis
• •2. Elevated serum SMRP levels (\>1.0 nM/L).
• •Free flowing pleural effusion requiring management by placement of a pleural catheter. Patients with a functional pleural catheter already in place are eligible for the study, as long as there are no clinical concerns of infection.
• •OR
• •No free-flowing pleural effusion: an Interventional Radiologist has agreed that radiology-guided intrapleural or peritumoral injection of the CAR T cells is feasible.
• •Chemotherapy, targeted therapy (such as a tyrosine kinase inhibitor) or therapeutic radiotherapy must have been completed at least 14 days prior to administration of T cells. Continuation of hormonal therapy (ie for breast cancer) is acceptable. Prior immunotherapy with checkpoint blockade (i.e. PD1 inhibitor, PDL1 inhibitor or CTL4-antagonist or similar agent) must have been completed more than 1 month1prior to the T cell infusion.
• •Chemotherapy must have been completed at least 7 days prior to leukapheresis
• •Palliative radiotherapy must be completed at least 2 days prior to administration of cyclophosphamide
• •Any major thoracic (thoracotomy with lung or esophageal resection) or abdominal (laparotomy with organ resection) operation must have occurred at least 28 days before study enrollment. Patients who have undergone diagnostic VATS or laparoscopy can be included in the study.
• •All acute toxic effects of any previous therapeutic or palliative radiotherapy, chemotherapy, or surgical procedures must have resolved to grade I or lower according to CTCAE (version 4.0).
• •Lab requirements (hematology)
• •White blood cell (WBC) count ≥3000 cells/mm3
• •Absolute neutrophil count ≥1500 neutrophils/mm3
• •Platelet count ≥100,000 platelets/mm3 Lab requirements (serum chemistry)
• •Bilirubin ≤ 1.5x upper limit of normal (ULN)
• •Serum alanine aminotransferase and serum aspartate aminotransferase (ALT/AST) ≤.5x ULN
• •Serum creatinine ≤ 1.5x ULN or Cr \> 1.5x ULN, but calculated clearances of \>60
• •Negative screen for human immunodeficiency virus (HIV), hepatitis B virus (HBV) antigen, and hepatitis C virus (HCV). If testing was performed during the previous 3 months, there is no need to repeat testing, as long as documentation of results is provided to the study site. Subjects must receive counseling and sign a separate informed consent form for HIV testing.
• •Subjects and their partners with reproductive potential must agree to use an effective form of contraception during the period of drug administration and for 4 weeks after completion of the last administration of the study drug. An effective form of contraception is defined as oral contraceptives plus 1 form of barrier or double-barrier method contraception (condom with spermicide or condom with diaphragm).
• •Subjects must be able to understand the potential risks and benefits of the study and must be able to read and provide written, informed consent for the study