Phase II trial of a DNA vaccine encoding prostatic acid phosphatase (pTVG-HP) and nivolumab (Nivo) in patients (pts) with nonmetastatic, PSA-recurrent prostate cancer (PCa).

Abstract

TPS273 Background: Radical prostatectomy (RP) and radiation therapy (RT) are the gold standard, curative intent treatment for pts with presumed organ-confined PCa. However, about one third of these pts will have progressive or metastatic disease at 10 years (yr). Pts with PSA recurrence without radiographic evidence of metastatic (m) PCa (stage M0) will ultimately develop radiographically apparent mPCa within a median of 8 yr. Pts with rapid PSA doubling time (DT) have a markedly shorter time to mPCa and death. Utilizing an immunotherapeutic approach could utilize the sensitivity and specificity of the immune system to treat microscopic disease and potentially avoid or postpone androgen deprivation therapy (ADT) and its unwanted side effects. Methods: In this single arm, two-stage phase II trial, a total of 21-41 PCa pts with PSA only progression (4 rising PSA with final PSA ≥ 2 ng/mL) after initial RP for presumed organ-confined disease who have no radiographic evidence of mPCa in conventional imaging (CT and bone scan) will be enrolled. Pts with small cell or other variant PCa, or history of ADT other than concurrent with RT are excluded. All pts will be treated with pTVG-HP 100 μg intradermally (id) and Nivo 240 mg IV every (Q) 2 weeks (w) x6, and then pTVG-HP 100 μg id and Nivo 480 mg IV Q4w x9 beginning w12 on study. Pts with PSA on w4 > PSA on day 1 will additionally receive rhGM-CSF 208 μg id, as a vaccine adjuvant, Q2w x4 beginning w4 on study. Pts will be treated until progression or up to a total of 1 yr. Response will be monitored by CT and bone scan Q6 months or as clinically indicated. Primary endpoints are safety and tolerability of this combination and PSA complete response rate (PSA < 0.2 ng/mL). Key secondary endpoints are 2-yr metastasis-free survival, median radiographic progression-free survival, PSA response rate (≤50% of baseline), and changes in PSA DT. Elicited antigen-specific T-cell and/or IgG response and its correlation with PSA response will be explored. Bone mets not detected by conventional imaging and their association with response will be evaluated by Quantitative Total Bone Imaging (QTBI) by NaF PET/CT. Updated enrollment will be presented. Clinical trial information: NCT03600350.