Long-term follow up of patients treated with a DNA vaccine (pTVG-HP) for PSA-recurrent prostate cancer

BackgroundWe have previously reported two single-agent phase I trials, evaluating dose or schedule, of a DNA vaccine (pTVG-HP) encoding prostatic acid phosphatase (PAP) administered with GM-CSF adjuvant. These were in patients with PSA-recurrent, radiographically non-metastatic, prostate cancer (Pca). Patients were followed long term for evidence of late adverse events. We report here the long-term safety and overall survival of these patients.Methods22 patients with non-metastatic, castration sensitive Pca (nmCSPC) were treated with pTVG-HP, 100-1500 μg, administered over 12 weeks, and followed for 15 years. 17 patients with non-metastatic castration-resistant Pca (nmCRPC) were treated with 100 μg pTVG-HP with different schedules over one year, and followed for 5 years. Subsequent treatments, adverse events possibly attributable to treatment, and overall survival were collected. Available long-term blood samples were evaluated for immune response to the PAP target antigen.ResultsNo adverse events were detected in long-term follow-up that were deemed possibly related to pTVG-HP treatment. Patients with nmCSPC had a median overall survival of 12.3 years, with 5/22 (23%) alive at 15 years. 8/22 (36%) died due to prostate cancer with a median survival of 11.0 years, and 9/22 (41%) died of other causes. The median time to the initiation of androgen deprivation was 3.1 years. The median time from androgen deprivation to the next therapy was 6.4 years. The median time to the development of metastases was 8.2 years. Patients with nmCRPC had a median overall survival of 4.5 years, with 8/17 (47%) alive at 5 years. The median time to development of metastases was 1.4 years, and the median time to next therapy was 2.1 years. The presence of T cells specific for the PAP target antigen was detectable in 7/10 (70%) individuals with nmCSPC, and 3/5 (60%) individuals with nmCRPC, many years after immunization.ConclusionsImmunization with pTVG-HP was not associated with late adverse events years after administration. The detection of immune responses to the vaccine target years after immunization suggests durable immunity can be elicited in some patients using a DNA vaccine encoding a tumor-associated antigen.Clinical trial identificationNCT00582140; NCT00849121.Legal entity responsible for the studyD.G. McNeel.FundingNational Institutes of Health and US Department of Defense.DisclosureD.G. McNeel: Financial Interests, Personal, Ownership Interest: Madison Vaccines Inc; Financial Interests, Institutional, Local PI: Janssen, OncoC4; Financial Interests, Institutional, Research Funding: Merck; Financial Interests, Institutional, Other, Drug support for clinical trial: BMS; Financial Interests, Personal, Advisory Role: Nuntius Therapeutics, PharmaJet. J. Eickhoff: Financial Interests, Personal, Other, Consultant: AbbVie, Amgen, Syneos Health; Financial Interests, Personal, Other, Consulting: Bluebird Bio, AIQ. G. Liu: Financial Interests, Personal, Ownership Interest: AIQ Solutions; Financial Interests, Institutional, Local PI: Pfizer, Janssen, Madison Vaccines Inc. All other authors have declared no conflicts of interest.