DNA vaccines INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12) were administered to biochemically recurrent prostate cancer patients (pts) to demonstrate breaking tolerance, assessing antigen-specific humoral and cellular immune responses with the potential for stabilization of disease progression.
Phase I, open-label, multi-center study in pts post-definitive therapy with a rising PSA after surgery and/or RT and PSA doubling time (DT)> 3 months (mos), testosterone > 150 ng/dL, no concomitant ADT and no evidence of metastases. Safety, immunogenicity and efficacy were evaluated in 4 treatment arms in 60 planned pts (A: 16, 2mg INO-5150; B: 15, 8.5 mg INO-5150; C: 15, 2mg INO-5150 + 1mg INO-9012; D: 16, 8.5mg INO-5150 + 1mg INO-9012) treated with 4 IM doses followed by electroporation on day 0, wks 3, 12 and 24 who were followed for a total of 72 Wks.
Median age, Gleason score and time since diagnosis were 69.5 yrs (range: 55.4-87.7), 7 (5-10) and 8.4 yrs (0.4-23.8) respectively. Of 61 evaluable pts, 38 (62%) had PSADT ≤ 12 mos and 23 (38%) had DT > 12 mos at Day 0. For pts with DT ≤ 12 mos, Day 0 and week 27 median DT were 6.0 (1.5, 11.6) mos and 8.1 (2.2, 100.0) mos respectively. Flow cytometry analysis revealed antigen specific upregulation of CD38 and Perforin on CD8+ T cells in 19/50 (38%) pts across the trial, with the greatest proportion in arm A, 8/14 (57%). Additional analysis for this cell subset showed a high PD-1 expression of 68.6% in this arm at week 27. Of note, in 8/15 (53%) arm A pts with DT ≤ 12 mos, their median DT at Day 0 was 6.2 (2.9, 10.2) mos and 19.2 (6.6, 100.0) mos at Wk 27. Safety: 7 Grade (Gr) 3 SAEs in 5 pts and 0 Gr 4-5 SAEs reported. Most AEs were Gr 1-3 in 51/62 (82%) pts and majority of those were associated with injection site reactions.
INO-5150 +/- INO-9012 was safe at dosages examined. Data demonstrated both PSA and PSMA are immunogenic and INO-5150 induced cellular immune responses. Higher proportion of arm A pts showed immunological responses as well as improvements in PSA DT, specifically pts with DT ≤ 12 mos suggesting correlation of immunological efficacy and clinical benefit. Continued analyses are planned as patient follow-up is ongoing. (NCT02514213)
Clinical trial identification
NCT02514213; July 29, 2015
Legal entity responsible for the study
K. Bhatt: Inovio (study sponsor employee), own stocks M. Morrow, T. McMullan, K. Kraynyak, J. Lee, B. Sacchetta, L. Liu, S. Rosencranz: Inovio (study sponsor) employee, own stocks in company. Y. Whang: Research funding from Janssen, Astellas, Tokai, Inovio. I. Csiki, M. Bagarazzi: Employed by Inovio Pharmaceuticals. All other authors have declared no conflicts of interest.