Phase 1/2 Dose-Escalation and Cohort Study of STEAP1 CART With Enzalutamide in Participants With mCRPC
This phase I/II trial tests the safety and effectiveness of cell therapy (STEAP1 CART) with enzalutamide in treating patients with prostate cancer that continues to grow despite surgical or medical treatments to block androgen production (castration-resistant) and that has spread from where it first started (the prostate) to other places in the body (metastatic). Prostate cancer is the second leading cause of cancer deaths in men. Localized prostate cancer is often curable and even metastatic disease may respond to treatment for a few years. Despite multiple therapies, including hormone therapy and chemotherapy, metastatic castration-resistant prostate cancer (mCRPC) still remains an incurable disease. Recently, adoptive cellular immunotherapies have been developed to transfer immunogenic cells to the patient to produce an anti-tumor response. Chimeric antigen receptor T (CART)-cell therapy is a type of treatment in which a patient's T-cells (a type of immune cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Prostate stem cell antigen and prostate specific membrane antigen CAR T cell therapies have been shown to be safe and effective, but objective tumor responses remain rare. STEAP1 is an antigen that promotes cancer growth and spread and is found to be broadly expressed in mCRPC tissues. STEAP1 CART is CAR T cells that have been engineered with a STEAP1 antigen to better target prostate tumor cells. Enzalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of cancer cells. Giving STEAP1 CART with enzalutamide may kill more tumor cells in patients with mCRPC.
• Tissue confirmation of prostate adenocarcinoma and STEAP1 expression. Confirmation of diagnosis must be or have been performed by internal pathology review of archival material at Fred Hutch/ University of Washington Medical Center (UWMC). Tissue will be stained by IHC to confirm STEAP1 expression
• Measurable disease by RECIST 1.1 criteria or bone only metastases with measurable PSA ( ≥ 1 ng/mL)
• Must have progressed (at least 2 rising PSA levels with at least a 1-week interval and a minimum PSA of 1.0 ng/mL, progression per RECIST 1.1, or 2 or more new bone lesions by bone scan), after becoming castration-resistant
• Have received, at any time, a CYP17 inhibitor or a second-generation antiandrogen therapy, and a taxane, or they must decline or be ineligible to receive these
• Castrate levels of testosterone (\< 50 ng/dL) with or without the use of androgen deprivation therapy
• 18 years or older at the time of enrollment
• Capable of understanding and providing a written informed consent
• Fertile male participants and their female partners must be willing to use an effective contraceptive method before, during, and for at least 4 months after the STEAP1 CART cell infusion
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Participants will be permitted to receive radiation therapy for palliative purposes throughout the study period, except during the 2-week period prior to undergoing leukapheresis
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) or estimated creatinine clearance \> 50 mL/min as calculated using the Cockcroft-Gault formula and not dialysis dependent
• Total bilirubin ≤ 1.5 x ULN. Participants with suspected Gilbert syndrome may be included if Total bilirubin (Bili) \> 3 mg/dL but no other evidence of hepatic dysfunction
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 5 x ULN
• ≤ grade 1 dyspnea and oxygen saturation (SaO2) ≥ 92% on ambient air
• If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, participants with forced expiratory volume in 1 second (FEVI) \>= 50% of predicted and diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) of \>= 40% of predicted will be eligible
• Participants \>= 60 years of age are required to have left ventricular ejection fraction (LVEF) evaluation performed within 1 year prior to lymphodepletion chemotherapy. LVEF may be established with echocardiogram or MUGA scan, and left ejection fraction must be \>= 35%. Cardiac evaluation for other participants is at the discretion of the treating physician
• Absolute neutrophil count (ANC) \> 1500 cells/ mm\^3
• Hemoglobin \> 9 g/dL
• Platelets \> 100,000 per mm\^3