PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer

Background: Immune checkpoint inhibitors interfere with the immune systems autoregulatory mechanisms, allowing for a potentially expanded and prolonged T-cell response with the possibility of greater antitumor effects. Nivolumab is a fully human Immunoglobulin G4 (IgG4) monoclonal antibody that targets the programmed cell death protein 1 (PD-1) protein. Specifically, the antibody binds to the PD-1 receptor and blocks its interaction with programmed death-ligand 1 (PD-L1) and programmed cell death 1 ligand 2 (PD-L2), thereby releasing PD-1 pathway-mediated inhibition of the immune response, including anti-tumor immune response. PROSTVAC (developed by the National Cancer Institute \[NCI\] and licensed to Bavarian Nordic Immunotherapeutics, Mountain View, California (CA) is a therapeutic cancer vaccine for prostate cancer. Early studies have demonstrated immunologic efficacy and suggested clinical benefit. A phase III trial has completed accrual. A previous study combining the immune checkpoint inhibitor ipilimumab and PROSTVAC suggested greater efficacy than PROSTVAC alone. Additional studies have demonstrated the potential efficacy of immunologic combination therapy with the immune checkpoint inhibitor nivolumab. This study will aim to evaluate the impact of the combination of PROSTVAC and the immune checkpoint inhibitor nivolumab on the tumor microenvironment focusing on immune cell infiltration as the primary endpoint. United States (US)-MRI imaging technology will be employed to sample the tumor before treatment and after radical prostatectomy. The findings from this study could serve as the basis for future studies with this combination in this population of participants and more advanced disease. Objectives: Safety (For castration resistant prostate cancer (CRPC) lead-in cohort) Evaluate changes in T-cell infiltration in the tumor after neoadjuvant treatment with PROSTVAC and nivolumab, relative to changes seen in a phase 2 trial with PROSTVAC alone in the neoadjuvant setting- NCT02153918 (For the neoadjuvant cohort). Eligibility: Participants must have histopathological documentation of adenocarcinoma of the prostate prior to starting this study and evaluable biopsy tissue (e.g., unstained slides or blocks) available for analysis. For the castration resistant lead in cohort, if histopathological documentation is unavailable, a rising prostate specific antigen (PSA) and a clinical course consistent with prostate cancer would be acceptable. Participants must have a performance status of 0 to 1 according to the Eastern Cooperative Oncology Group (ECOG) criteria. Hematological eligibility parameters (within 16 days of starting therapy): Granulocyte count 1,500/mm\^3 Platelet count 100,000/mm\^3 Hemoglobin (Hgb) \>= 8 g/dL Biochemical eligibility parameters (within 16 days of starting therapy): Hepatic function: Bilirubin \< 1.5 mg/dl (OR in participants with Gilbert's syndrome, total bilirubin \<= 3.0 mg/dL), aspartate aminotransferase (AST) and alanine transaminase (ALT) \<= 2.5 times upper limit of normal. Creatinine \<= 1.5 X ULN Design: The primary focus of this study will be to evaluate PROSTVAC and nivolumab in the neoadjuvant setting. Lead-in cohort evaluating the safety and tolerability of this combination in the castration resistant setting (CRPC cohort) Following this lead-in cohort in the CRPC setting, we will enroll a cohort in the neoadjuvant setting evaluating the combination of PROSTVAC and nivolumab. The lead-in safety cohort will require 10 participants and the neoadjuvant cohort will require 17 evaluable participants. In order to allow for a small number of inevaluable participants, the accrual ceiling will be set to 29 participants.