Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

PRIMARY OBJECTIVES: I. To evaluate the safety of pembrolizumab in combination with pTVG-HP (pTVG-HP plasmid DNA vaccine) in patients with castration-resistant, metastatic prostate cancer. II. To determine the 6-month progression-free survival and median time to radiographic progression in patients with castration-resistant metastatic prostate cancer treated with pembrolizumab in combination with pTVG-HP. III. To evaluate the anti-tumor response rates (objective response rate and prostate specific antigen \[PSA\] response rate, using Prostate Cancer Clinical Trials Working Group 2 \[PCWG2\] criteria) in patients with castration-resistant metastatic prostate cancer treated with pembrolizumab in combination with pTVG-HP. SECONDARY OBJECTIVES: I. To determine whether either treatment sequence, or prostatic acid phosphatase (PAP)-specific immune response, is associated with prolonged (6-month) radiographic progression-free survival. II. To evaluate effects of schedule (concurrent versus delayed administration of pembrolizumab) on the magnitude of PAP-specific T-cell responses, programmed death receptor-1 (PD-1) expression on circulating T cells, and ligands for PD-1 (PD-L1) expression on circulating epithelial cells (CEC) and on tumor biopsies. III. To determine the median time to radiographic progression using a concurrent administration schedule TERTIARY OBJECTIVES: I. To evaluate effects of treatment on number of circulating tumor cells. II. To evaluate PAP-specific antibody responses following treatment with pembrolizumab and pTVG-HP DNA vaccine (pTVG-HP plasmid DNA vaccine). III. To determine whether either treatment sequence elicits immunologic antigen spread to other prostate-associated antigens. IV. To determine whether pre-existing or vaccine-induced PD-L1 expression on CEC or tumor biopsies is predictive of objective clinical response. V. To determine whether treatment elicits expression of other regulatory molecules on tumor-specific T cells (e.g. hepatitis A virus cellular receptor 2 \[TIM3\], B and T lymphocyte associated \[BTLA\], and lymphocyte-activation gene 3 \[LAG3\]) or tumor cells (e.g. tumor necrosis factor receptor superfamily, member 14 \[HVEM\], phosphatidyl serine, ligands for programmed death receptor-2 \[PD-2\] \[PD-L2\]). VI. To determine whether PD-1-regulated antigen-specific T cells identified by trans vivo delayed-type hypersensitivity (DTH) testing can identify patients who develop objective clinical responses with PD-1 blockade therapy in combination with pTVG-HP. VII. To determine whether changes in lymph nodes and soft tissue tumor lesions are observed by fluorothymidine F-18 (FLT) positron emission tomography (PET)/computed tomography (CT) after treatment with vaccine with or without pembrolizumab. VIII. To determine if PD-1 inhibitor therapy in combination with pTVG-HP will change number and activity (SUV) in osteoblastic metastases as measured by NaF PET/CT. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive pTVG-HP plasmid DNA vaccine intradermally (ID) every other week on days 1, 15, 29, 43, 57, and 71 and pembrolizumab intravenously (IV) over 30 minutes every 3 weeks on days 1, 22, 43, and 64. ARM II: Patients receive pTVG-HP plasmid DNA vaccine ID as in Arm I and pembrolizumab IV over 30 minutes every 3 weeks on days 85, 106, 127, and 148. After completion of study treatment, patients are followed up 3, 6, 9, and 12 months and then annually for 2 years. ARM III: Extended Treatment. Patients received pTVG-HP + Pembrolizumab Extended Treatment ARM IV: Extended Treatment. Patients receive pTVG-HP every two weeks, and Pembrolizumab every 4 weeks