Neoantigen DNA Vaccine in Combination With Nivolumab/Ipilimumab and PROSTVAC in Metastatic Hormone-Sensitive Prostate Cancer

-Replication-competent vaccinia virus which has been engineered to encode the sequences for a modified human prostate-specific antigen (PSA) and a triad of co-stimulatory molecules (TRICOM)

-Fowlpox virus which does not replicate in human cells and has been engineered to encode the same sequences present in PROSTVAC-V.

-Nivolumab is a human monoclonal antibody (mAb)

-Ipilimumab is a mAb blocking the inhibitory signal mediated by cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4), a protein receptor that downregulates the immune system.

Each DNA vaccination will be 1 mL vaccine administered intramuscularly. At each vaccination time point, patients will receive two injections at separate sites.

-Electroporation device

-Pre-treatment, post-treatment A (optional), and end of treatment

-At the time of pre-treatment biopsy, mid-treatment of chemo-ADT, at time of enrollment (prior to POSTVAC administration), mid-treatment A, mid-treatment B (multiple)

-Post chemo/pre-treatment A, post-treatment A, pre-treatment B, post-treatment B

"* Post-treatment A/pre-treatment B~* Mid-Treatment B, after Cycle 9 Day 1 and prior to Cycle 10 Day 1~* End of treatment"