1. The following tests may be obtained any time prior to enrollment: Pathological confirmation of diagnosis and PSA expression in either the Laboratory of Pathology at NIH Clinical Center, Walter Reed National Military Medical Center at Bethesda. However, if no pathologic specimen is available, patients may enroll with a pathologist’s report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease. 2. The following parameters will be obtained within 8 weeks prior to enrollment: HIV test Hepatitis B and C 3. The following parameters will be obtained within 30 days prior to enrollment: Tc-99 whole body scintigraphy CT of chest/abdomen /pelvis (MRI may be substituted at investigator’s discretion). History and physical examination with ECOG Serum PSA Complete blood count plus differential and platelet count Hepatic and Acute Care panels Testosterone level 2.3 REGISTRATION PROCEDURES Registration and status updates (e.g., when a participant is taken off protocol therapy and when a participant is taken off-study) will take place per CCR SOP ADCR-2, CCR Participant Registration & Status Updates found here. 2.3.1 Treatment Assignment and Randomization/Stratification Procedures Cohorts Number Name Description 1 Prostate Cancer Patients Patients with chemotherapy naïve metastatic castrate-resistant prostate cancer 23 Short Title: Enzalutamide Vaccine in mCRPC Version Date: 03/29/2022 Arms Number Name Description 1 A Enzalutamide alone 2 B Enzalutamide with PSA-TRICOM Stratifications Name Distinct Options Notes Prior Immunotherapy Yes No Randomization and Arm Assignment Patients must be registered with Central Registration Information Services within 24 hours after signing the consent. All Patients on study will be directly assigned to cohort 1.