 A safety lead-in for each treatment arm will be performed prior to full 1:1 randomization into each arm. Definitive RT to the whole prostate gland will be delivered via high-dose rate HDR brachytherapy on Day 1 and Day 8 7 days of Cycle 1 pembrolizumab in each arm. Immediately before RT, SD-101 will be delivered to the dominant prostatic lesion on Day 1 and Day 8 7 days of Cycle 1 pembrolizumab in Arm 2. SD-101 will be administered intratumorally in concert with placement of the HDR brachytherapy catheters. Pembrolizumab will be continued for a total of 13 cycles, until disease progression, or unacceptable toxicity, whichever occurs first. Patients will receive 3 months of androgen deprivation therapy ADT run-in, followed by combined androgen blockade CAB for 9 months, then discontinuation of ADT. Primary outcome is to evaluate the rate of prostate specific antigen PSA nadir 2 ngmL at 15 and 24 month from the start of treatment among patients with non-castrate levels of testosterone 150 ngdL. Serum, archival prostate biopsy, mandatory baseline metastatic tumor biopsy, and optional repeat biopsy at time of progression, will be obtained to characterize circulating and intratumoral immune responses. 