1415P Phase II trial of a DNA vaccine with nivolumab in patients with PSA-recurrent, castration-sensitive prostate cancer (nmCSPC)

Abstract

We previously reported a trial of a DNA vaccine encoding prostatic acid phosphatase (PAP, pTVG-HP) with pembrolizumab in patients with metastatic, castration-resistant prostate cancer. The current trial evaluated a similar approach in patients with earlier stage prostate cancer, without evidence of metastases (nmCSPC). Patients with nmCSPC were treated with pTVG-HP and nivolumab every 2 weeks for 12 weeks, and then every 4 weeks, for 1 year total. Patients were then followed an additional year off treatment. The trial was designed as a single-arm 2-stage phase 2 trial with the primary endpoints being safety and complete PSA response rate. Secondary objectives included immune evaluations, 2-year MFS, median rPFS, and changes in PSA. No patients achieved a complete PSA response, and the trial was stopped after 19 patients were accrued to the first phase. Treatment was without unexpected toxicity. Median PSA doubling time (DT) pre-treatment was 5.9 months, and significantly increased (25.6 months, p=0.001) during the 12-month treatment period. PSA DT decreased in the 1-year post-treatment period (14.2 months). 3 patients (16%) had PSA declines from baseline > 50%, and 5 (26%) had PSA declines > 25%. 8/19 (42%) patients developed PAP-specific IFNγ- and/or granzyme B-secreting T cells, which tended to occur in patients with favorable change in PSA DT. While long-term follow up continues for several patients, with a median follow-up time of 13.8 months, 2 patients (11%) have had radiographic progression within 2 years. PD-1 pathway inhibitors alone have demonstrated little clinical activity for prostate cancer. Our findings demonstrate that combining PD-1 blockade with the T-cell activating agent pTVG-HP is safe, and can augment tumor-specific T cells that can result in prolonged stable disease. The absence of complete PSA responses, and the finding that PSA rise recurred after treatment, suggest that either longer therapy, or additional treatments, are required to optimize response. Ongoing and planned trials are assessing vaccines encoding multiple target antigens and/or using combined T-cell checkpoint blockade.