177^Lu-PSMA-617 in Combination With Sipuleucel-T for the Treatment of Metastatic Castration-Resistant Prostate Cancer

PRIMARY OBJECTIVE: I. To evaluate the immune response induced by the combination of lutetium Lu 177 vipivotide tetraxetan (177\^Lu-PSMA-617) and sipuleucel-T, using changes in anti-prostatic acid phosphatase (PAP) immunoglobulin G (IgG) antibody titers. SECONDARY OBJECTIVES: I. To evaluate anti-PA2024 antibody titers in patients receiving 177\^Lu-PSMA-617 alone versus in combination with sipuleucel-T. II. To assess the safety and tolerability of 177\^Lu-PSMA-617 plus sipuleucel-T. III. To evaluate the clinical efficacy of 177\^Lu-PSMA-617 alone versus in combination with sipuleucel-T. EXPLORATORY OBJECTIVES: I. To characterize the pharmacokinetics (PK) of 177\^Lu-PSMA-617 plus sipuleucel-T in the blood. II. To determine the impact of 177\^Lu-PSMA-617 in combination with sipuleucel-T on systemic immunomodulation. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A (CONTROL GROUP): Patients receive 177\^Lu-PSMA-617 intravenously (IV). Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, PSMA positron emission tomography (PET)/computed tomography (CT), bone scan, and magnetic resonance imaging (MRI) throughout the study. Additionally, patients may undergo MRI or CT of the brain throughout the study. ARM B (EXPERIMENTAL GROUP): Patients receive 177\^Lu-PSMA-617 IV. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Starting during week 8 of treatment, patients receive sipuleucel-T IV over 1 hour. Treatment repeat every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo leukapheresis, blood sample collection, PSMA PET/CT, bone scan, and MRI throughout the study. Additionally, patients may undergo MRI or CT of the brain throughout the study. After completion of study treatment, patients are followed up at 30 days, every 3 months for up to 1 year then every 6 months until progression followed by survival follow until death or withdrawal of consent.