Phase II Trial of a DNA vaccine encoding prostatic acid phosphatase (pTVG-HP [MVI-816]) in patients with progressive, nonmetastatic, castration-sensitive prostate cancer

Douglas G. McNeel, Jens C. Eickhoff, Laura E. Johnson, Alison R. Roth, Timothy G. Perk, Lawrence Fong, Emmanuel S. Antonarakis, Ellen Wargowski, Robert Jeraj, Glenn Liu

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE We previously reported the safety and immunologic effects of a DNA vaccine (pTVG-HP [MVI-816]) encoding prostatic acid phosphatase (PAP) in patients with recurrent, nonmetastatic prostate cancer. The current trial evaluated the effects of this vaccine on metastatic progression. PATIENTS AND METHODS Ninety-nine patients with castration-sensitive prostate cancer and prostate-specific antigen (PSA) doubling time (DT) of less than 12 months were randomly assigned to treatment with either pTVGHP co-administered intradermally with 200 mg granulocyte-macrophage colony-stimulating factor (GM-CSF) adjuvant or 200 mg GM-CSF alone six times at 14-day intervals and then quarterly for 2 years. The primary end point was 2-year metastasis-free survival (MFS). Secondary and exploratory end points were median MFS, changes in PSA DT, immunologic effects, and changes in quantitative 18F-sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) imaging. RESULTS Two-year MFS was not different between study arms (41.8% vaccine v 42.3%; P = .97). Changes in PSA DT and median MFS were not different between study arms (18.9 v 18.3 months; hazard ratio [HR], 1.6; P = .13). Preplanned subset analysis identified longer MFS in vaccine-treated patients with rapid (, 3 months) pretreatment PSA DT (12.0 v 6.1 months; n 5 21; HR, 4.4; P = .03). PAP-specific T cells were detected in both cohorts, including multifunctional PAP-specific T-helper 1-biased T cells. Changes in total activity (total standardized uptake value) on 18F-NaF PET/CT from months 3 to 6 increased 50% in patients treated with GMCSF alone and decreased 23% in patients treated with pTVG-HP (n = 31; P = .07). CONCLUSION pTVG-HP treatment did not demonstrate an overall increase in 2-year MFS in patients with castration-sensitive prostate cancer, with the possible exception of a subgroup with rapidly progressive disease. Prespecified 18F-NaF PET/CT imaging conducted in a subset of patients suggests that vaccination had detectable effects on micrometastatic bone disease. Additional trials using pTVG-HP in combination with PD-1 blockade are under way.

Original languageEnglish (US)
Pages (from-to)3507-3517
Number of pages11
JournalJournal of Clinical Oncology
Volume37
Issue number36
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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