PSCA-CAR T Cells in Treating Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer

PRIMARY OBJECTIVES: I. Define the safety and tolerability of autologous anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T lymphocytes (PSCA-CAR T cells) in patients with PSCA+ metastatic castration resistant prostate cancer (mCRPC). II. Define the recommended phase 2 dose (RP2D) of PSCA-CAR T cells in patients with PSCA+ mCRPC. SECONDARY OBJECTIVES: I. Assess the expansion and persistence of PSCA-CAR T cells. II. Assess clinical response based on Prostate Cancer Working Group 3 (PCWG3) criteria. III. Assess survival outcomes (including biochemical progression free survival \[PFS\], radiographic PFS and overall survival \[OS\]). IV. Assess serum cytokine profiles in peripheral blood pre- and post-therapy. V. Describe the PSCA expression level on tumor cells prior to CAR T cell infusion, and the relationship it may have with disease response and observed toxicities. EXPLORATORY OBJECTIVES: I. Characterize the phenotypes and frequencies of immune cell subsets in the peripheral blood pre- and post-therapy. II. Enumerate and characterize tumor-infiltrating lymphocytes (TILs) pre- and post-therapy. III. Enumerate and analyze gene expression of circulating tumor cells (CTC) pre- and post-therapy. IV. Analyze circulating cell-free DNA (cfDNA). V. Determine the immunogenicity of PSCA-CAR T cells. OUTLINE: This is a dose-escalation study. Patients may receive lymphodepleting regimen at the discretion of the treating physician including fludarabine intravenously (IV) on days -5 to -3 and cyclophosphamide IV on days -5 to -3 or on days -4 and/or -3. Patients then receive autologous anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T lymphocytes IV over 10-15 minutes at day 0. After completion of study treatment, patients are followed up at day 1, every 2 days for up to 14 days, weekly for up to 1 month, every month for up to 1 year, and then annually for up to 15 years.