Abstract 1415P
Background
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).
Methods
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.
Results
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.
Conclusions
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.
Clinical trial identification
NCT03600350.
Editorial acknowledgement
Legal entity responsible for the study
Douglas G. McNeel, MD PhD.
Funding
University of Wisconsin Carbone Cancer Center.
Disclosure
D.G. McNeel: Financial Interests, Personal, Ownership Interest: Madison Vaccines Inc.; Financial Interests, Institutional, Principal Investigator: BMS, Novartis, Harpoon Therapeutics, Janssen; Financial Interests, Personal, Advisory Role: CellVax. H. Emamekhoo: Financial Interests, Personal, Advisory Board: Exelixis, Seattle Genetics. J. Eickhoff: Financial Interests, Personal, Advisory Role: AbbVie, Amgen, Bluebird Bio, AIQ. G. Liu: Financial Interests, Personal, Ownership Interest: AIQ Solutions; Financial Interests, Institutional, Principal Investigator: MVI, Concept, Pfizer; Financial Interests, Personal, Advisory Board: Janssen. All other authors have declared no conflicts of interest.