Human Chimeric Antigen Receptor Modified T-Cells with or without Cyclophosphamide in Treating Patients with Mesothelin-Expressing Cancers

Inclusion Criteria

• Histologically confirmed cancer (one of the following): * Cohorts 1-4 patients: ** Metastatic or recurrent lung adenocarcinoma. ** Persistent or recurrent serous epithelial ovarian cancer or primary peritoneal carcinoma or fallopian tube carcinoma. ** Malignant pleural and peritoneal mesothelioma (histologically confirmed epithelial). * Cohort 5 patients: ** Metastatic or recurrent lung adenocarcinoma with documented pleural effusion. ** Persistent or recurrent serous epithelial ovarian cancer or primary peritoneal carcinoma or fallopian tube carcinoma with documented pleural effusion. ** Malignant pleural and peritoneal mesothelioma (histologically confirmed epithelial) with documented pleural effusion.
• Confirmation of tumor mesothelin expression (>= 50% of tumor cells).
• Failure of at least one prior standard of care chemotherapy for advanced stage disease. Prior therapies against PD-1 or PDL-1 are permissible if > 4 weeks from enrollment.
• Subjects must have measurable disease as defined by RECIST 1.1 criteria or modified RECIST criteria.
• Patients with asymptomatic central nervous system (CNS) metastases that have been treated and are off steroids are allowed. They must meet the following at the time of enrollment: * No concurrent treatment for the CNS disease. * No progression of CNS metastasis on magnetic resonance imaging (MRI) at screening scans. * No evidence of leptomeningeal disease or cord compression.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Absolute neutrophil count >= 1,000/ul.
• Platelets >= 75,000/ul.
• Hemoglobin >= 9 g/dL.
• Bilirubin =< 2.0 x the institutional normal upper limit unless secondary to bile duct obstruction by tumor.
• Creatinine =< 1.5 x the institutional normal upper limit.
• Albumin >= 2.
• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 5 x the institutional normal upper limit.
• Cardiac ejection fraction of >= 40% as measured by resting echocardiogram, with no clinically significant pericardial effusion.
• Blood coagulation parameters: Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 and a partial prothrombin time (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.
• Provides written informed consent.
• Subjects of reproductive potential must agree to use acceptable birth control methods.

Exclusion Criteria

• Sarcomatoid mesothelioma histology which is known in the literature to not express mesothelin; biphasic mesothelioma is also excluded.
• Known leptomeningeal carcinomatosis or spinal cord compression. Screening for this is not required unless suspicious symptoms.
• Patients with symptomatic CNS metastases are excluded.
• Participation in a therapeutic investigational study within 4 weeks prior to enrollment, or anticipated treatment with another investigational product while on study. This refers to non-commercially approved investigational drugs different than those used in this protocol.
• Active invasive cancer other than the one of the three cancers in 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.
• Human immunodeficiency virus (HIV) infection.
• Active hepatitis B or hepatitis C infection.
• 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 enrollment visit, with the exception of thyroid replacement.
• Patients with ongoing or active infection.
• Planned concurrent treatment with systemic high dose corticosteroids. Patients may be on a stable low dose of steroids (< 10 mg equivalent of prednisone) for chronic respiratory conditions or adrenal insufficiency. Corticosteroids treatment as anti-emetic prophylaxis on the day of cyclophosphamide administration is allowed per institutional guidance.
• Patients requiring supplemental oxygen therapy.
• Prior therapy with lentiviral gene modified cells.
• 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.
• Any clinically significant pleural or peritoneal effusion that cannot be drained with standard approaches. An indwelling drainage device placed prior to enrollment is acceptable.
• Pregnant or breastfeeding women.