Background In murine studies, we demonstrated that a DNA vaccine encoding the androgen receptor (pTVG-AR) given prior to androgen deprivation elicited prostate tumor-infiltrating lymphocytes and an antitumor response. The current trial evaluated this approach, with or without programmed cell death protein-1 (PD-1) blockade, in patients with high-risk newly diagnosed prostate cancer. Methods In the first stage of a two-stage protocol, 24 patients were randomized to treatment with (1) degarelix alone (n=6); (2) pTVG-AR followed by degarelix (n=9); or (3) pTVG-AR, degarelix and nivolumab (n=9), each delivered over 12 weeks prior to prostatectomy. The primary objectives were safety and pathological complete response or minimal residual disease (MRD). Secondary endpoints were residual cancer burden (RCB) <0.25 cm 3 and 1-year prostate-specific antigen (PSA) progression-free survival. Results Adverse events were almost exclusively in Arm 3, attributed to nivolumab. One patient achieved MRD (Arm 2), and three patients had an RCB <0.25 cm 3 (all in Arm 2). At 1 year after surgery, the PSA progression-free survival rate was 33% (2/6) in Arm 1, 89% (8/9) in Arm 2, and 33% (3/9) in Arm 3 (p=0.039). Tissue analysis at prostatectomy demonstrated reduced CD4+cells with a regulatory phenotype in patients in Arm 2. Conclusion In this first stage of a pilot study that awaits confirmation with larger numbers of patients, our results suggest that vaccination targeting AR given prior to androgen deprivation therapy might improve outcome for patients with high-risk prostate cancer. Contrary to our initial hypothesis, this was not improved with the addition of PD-1 blockade, possibly due to the activation of regulatory CD4+T cells. Trial registration number NCT04989946 .
Jarrard et al. (2026) studied this question.