17PD - INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12) Immunotherapy in Biochemically Relapsed Prostate Cancer (17PD)

Date 09 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Poster Discussion session
Topics Cancer in Pregnancy
Cancer in Special Situations
Gynaecologic Malignancies
Presenter Ildiko Csiki
Citation Annals of Oncology (2017) 28 (suppl_11): xi3-xi5. 10.1093/annonc/mdx710
Authors I. Csiki1, N. Shore2, K. Bhatt1, M. Morrow1, K. Kraynyak1, L. Liu1, T. McMullan1, J. Lee1, B. Sachetta1, S. Rosencranz1, E. Heath3, M. Bagarazzi1
  • 1Clinical Development, Inovio Pharmaceuticals, 19464 - Plymouth Meeting/US
  • 2Urology, Carolina Urologic Research Center, 29572 - Myrtle Beach/US
  • 3Wayne State Research Institute, Karmanos Cancer Insitute, Detroit/US

Abstract

Background

INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12) immunotherapy was administered to biochemically recurrent prostate cancer patients (pts) to demonstrate breaking tolerance and assess antigen-specific humoral and cellular immune responses for stabilization of disease progression.

Methods

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.

Results

Across all cohorts, among evaluable pts, 35/58 (60%) had IFN-γ reactivity by ELISPOT. Antibody titers against PSA and PSMA were observed in 6/61 (10%) and 5/61 (8%) pts respectively. 19/50 (38%) pts across the trial had CD38 and Perforin + CD8 T cell responses with the greatest proportion in arm A, 8/14 (57%) as well as a high PD-1 expression of 68.6% in this arm at week 27. Pts with immune reactivity had dampening of % PSA rise (median: 28.0 vs 53.4, p = 0.02) compared to non-reactive pts. Myeloid derived stem cell (MDSC) assessment showed that the frequency of MDSCs is decreased in pts with >70% PSA decline compared to pts with radiographically confirmed disease progression. Median Day 0 PSADT improved from 8.2 to 19.0 months (mos) (p = 0.002) for all cohorts combined at last observation with highest numerical improvement in Cohort A (26.6 mos). 56/61 (90%) pts are metastasis free at median follow-up of 436 days (85-582). Safety summary: 11 Grade (Gr) 3 SAEs in 6 pts reported. 82% of pts had Gr 1-3 AE’s primarily related to injection site reactions.

Conclusions

INO-5150 +/- INO-9012 was safe and well tolerated. Data demonstrated both PSA and PSMA are immunogenic and INO-5150 induced cellular immune responses. Additional analyses and follow-up are ongoing to further elucidate the correlation of immunologic efficacy and clinical benefit that has been initially observed.

Clinical trial identification

NCT02514213

Legal entity responsible for the study

Inovio Pharmaceuticals

Funding

Inovio Pharmaceuticals

Disclosure

I. Csiki, K. Bhatt, M. Morrow, K. Kraynyak, L. Liu, T. McMullan, J. Lee, B. Sachetta, S. Rosencranz, M. Bagarazzi: Employee of Inovio Pharmaceuticals. All other authors have declared no conflicts of interest.