If unresolved, the Monitor will request that the site Staff enter the deviations in the CCR Protocol Deviation Tracking System (PDTS) for deviation reporting to the Sponsor and as applicable per institutional and IRB guidance. 9 STATISTICAL CONSIDERATIONS The primary objective is to determine if PSA-TRICOM combined with enzalutamide will increase time to progression in chemotherapy-naïve metastatic castration resistant prostate cancer patients compared to enzalutamide alone. Secondary objectives include determining if PSA-TRICOM combined with enzalutamide will increase overall survival and/ or delay PSA progression compared to enzalutamide alone, and. Tumor growth rates at various time points will also be determined and compared as a secondary objective. Exploratory objectives include comparing the immune response in patients between the two arms. Immune response evaluation will include CD4 cells, CD 8 cells, PSA-specific T-cells, natural killer cells, Regulatory T-cells, Regulatory T-cell function, cytokines, naïve thymic emigrants. The study will also aim to determine the association between immunologic parameters and clinical outcomes The study is based on an assumption of a median time to progression of 10 months in chemotherapy-naïve mCRPC patients. Should the PREVAIL trial results be reported prior to the opening of this trial, and if they are substantially different from this estimate, adjustments in this plan will be made accordingly. The primary endpoint will be the comparison of the Kaplan- Meier curves for the two arms using a stratified log-rank test. The trial will be conducted using a phase 2.5 design (one tailed 0.10 alpha level test) [41]. If we assume that the arms will have time to progression medians of 10 vs. 18 cycles (which would have hazards of 0.0693 and 0.0385, respectively, and a hazard ratio of 1.80), and if patients are accrued for 36 months and the last one enrolled is followed for up to 12 more months (48 months total follow-up from time of enrolling first patient), and a total of 52 events are observed, then 36 patients per arm provides 80% power to compare the two arms. Patients will be stratified based on previous immunotherapy used as cancer treatment. 56 Short Title: Enzalutamide Vaccine in mCRPC Version Date: 03/29/2022 Survival will be compared between the two arms, as a secondary endpoint, using Kaplan-Meier curves and a stratified log-rank test. Continuous parameters will be compared between the two arms using appropriate non-parametric tests, such as a Wilcoxon rank sum test.