A Study of CART-PSMA-TGFβRDN in Patients With Metastatic Castration Resistant Prostate Cancer

Inclusion Criteria: * Confirmed histologic diagnosis of prostate cancer and have mCRPC, with castrate levels of testosterone (\<50 ng/mL) * PSA measurable disease per Prostate Working Group 3 (PCWG3) criteria * Prior therapies defined as at least 2 prior lines of systemic therapy for prostate cancer, including at least one second generation androgen receptor inhibitor and/or CYP17α inhibitor. At least one line of prior therapy must be in the mCRPC setting * Estimated estimated glomerular filtration rate ≥ 60 mL/min by Modification of Diet in Renal Disease criteria * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5x the upper limit of normal (ULN); patients with hepatic metastases ALT and AST ≤ 3.0 x ULN * Serum total bilirubin \< 1.5 mg/dL unless patient has known Gilbert's Syndrome, then serum bilirubin ≤3 mg/dL * Serum albumin ≥ 3.0 g/dL * Left ventricular ejection fraction (LVEF) ≥ 50%. LVEF assessment must have been performed within 8 weeks of enrollment * Hemoglobin ≥ 8 g/dL * Absolute neutrophil count ≥ 1000/μL * Platelet count ≥ 75,000/μL * Patients who have not undergone bilateral orchiectomy must be able to continue gonadotropin-releasing hormone (GnRH) therapy during the study * Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 * Toxicities from any previous therapy must have recovered to Grade 1 or baseline * Patients of reproductive potential agree to use of approved highly effective contraceptive methods Exclusion Criteria: * Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to screening, unless treated with curative intent * Current treatment with systemic corticosteroids (defined as a dose greater than the equivalent of prednisone 10 mg/day) * Active autoimmune disease (including connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease or multiple sclerosis) or a history of severe autoimmune disease requiring prolonged immunosuppressive therapy (any immunosuppressive therapy within 6 weeks prior to screening visit) * Current human immunodeficiency virus (HIV), hepatitis C virus, hepatitis B virus infections; Patients who are hepatitis B core antigen positive, hepatitis B surface antigen negative, should have a quantitative viral load measured; If viral load is undetectable, the patient will not be excluded if hey are able to be treated with anti-viral medication for at least 7 days prior to lymphodepletion until at least 6 months after infusion with viral load and ALT monitoring * Active or uncontrolled medical or psychological condition that would preclude participation * History of seizure disorder * Prior allogeneic stem cell transplant * Central nervous system malignancy * History of severe infusion reaction to monoclonal antibodies or biological therapies, or to study product excipients that would preclude the patient safely receiving CART-PSMA-TGFβRDN cells * History of being previously treated with a J591 antibody-based therapy * Ferritin levels ≥ 4x the upper limit of normal prior to apheresis or prior to the start of lymphodepleting chemotherapy * Active or recent (within the past 6 months prior to apheresis or lymphodepletion) cardiovascular disease, defined as (1) New York Heart Association Class III or IV heart failure, (2) unstable angina, (3) a history of recent (within 6 months) myocardial infarction or sustained (\> 30 second) ventricular tachyarrhythmias, or (4) cerebrovascular accident * Any active infection currently being treated or any infection within the last 6 weeks that required 7 days or more of IV antibiotics or any active infection within the last 4 weeks that requires use of oral antibiotics. Patients may be eligible once these timeframes elapse and with evidence that the infection has completely resolved * Have inadequate venous access for or contraindications for the apheresis procedure * Must agree not to participate in a conception process or must agree to a highly effective method of contraception