CART-PSMA-TGFβRDN Cells for Castrate-Resistant Prostate Cancer

Inclusion criteria

• Metastatic castrate resistant prostate cancer
• RETIRED WITH PROTOCOL VERSION 15
• Radiographic evidence of osseous metastatic disease and/or measurable, non-osseous metastatic disease (nodal or visceral)
• Patients ≥ 18 years of age
• ECOG performance status of 0 - 1
• Adequate organ function, as defined by:

• Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 cc/min
• Serum total bilirubin < 1.5x ULN
• Serum ALT/AST < 2x ULN
• Adequate hematologic reserve within 4 weeks of eligibility confirmation by physician-investigator as defined by:

• Hgb > 10 g/dl
• PLT > 100 k/ul
• ANC > 1.5 k/ul Note: Subjects must not be transfusion dependent
• Evidence of progressive castrate resistant prostate adenocarcinoma, as defined by:

• Castrate levels of testosterone (< 50 ng/ml) with or without the use of androgen-deprivation therapy AND
• Evidence of one of the following measures of progressive disease in the 12 weeks preceding eligibility confirmation by physician:

i. soft tissue progression by RECIST 1.1 criteria ii. osseous disease progression with 2 or more new lesions on bone scan (as per PCWG2 criteria) iii. increase in serum PSA of at least 25% and an absolute increase of 2 ng/ml or more from nadir (as per PCWG2 criteria)

• Prior therapy with at least one standard initial therapy for the treatment of metastatic castrate resistant prostate cancer (i.e. docetaxel chemotherapy, 17α lyase inhibitor, or second-generation anti-androgen therapy)
• Provides written informed consent
• Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion criteria

• RETIRED WITH PROTOCOL V16
• History of an active non-curative non-prostate primary malignancy within the prior 3 years
• RETIRED WITH PROTOCOL VERSION 6
• Subjects who require the chronic use of systemic corticosteroid therapy. Patients may be on a low dose of steroids (≤10mg equivalent of prednisone).
• RETIRED WITH PROTOCOL V13
• Subjects with Class III/IV cardiovascular disability according to the New York Heart Association Classification
• Subjects with symptomatic vertebral metastases affecting spinal cord function (as determined by clinical history, physical exam, or MRI imaging)
• Active autoimmune disease, including connective tissue disease, uveitis, inflammatory bowel disease, or multiple sclerosis; or a history of severe (as judged by the physician-investigator) autoimmune disease requiring prolonged immunosuppressive therapy
• Patients with ongoing or active infection.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
• Active hepatitis B, hepatitis C or HIV infection.
• Active medical condition that, in the opinion of the physician-investigator, would substantially increase the risk of uncontrollable CRS or CAR Neurotoxicity.