This study was a phase I, open-label, multi-center study among 61 patients post-definitive local therapy with a rising PSA after surgery and/or radiotherapy with a PSA doubling time > 3 months, testosterone > 150 ng/dL, no concomitant androgen deprivation therapy, and no evidence of metastases. Safety, immunogenicity and efficacy were evaluated in four treatment arms: Arm A: n=16, 2mg INO-5150; Arm B: n=15, 8.5 mg INO-5150; Arm C: n=15, 2mg INO-5150 + 1mg INO-9012; Arm D: n=16, 8.5mg INO-5150 + 1mg INO-9012, treated with four intramuscular doses followed by electroporation on day 0, weeks 3, 12 and 24 who were followed for a total of 72 weeks. For these 61 patients, the median age was 69.5 years (range: 55-88), median Gleason score was 7 (range: 5-10), and median time since diagnosis was 8.4 years (range: 0.4-23.8). 38 patients (62%) had a PSA doubling time ≤ 12 months and 23 (38%) had PSA doubling time > 12 months at Day 0. Flow cytometry analysis revealed antigen specific upregulation of CD38 and Perforin on CD8+ T cells in 19/50 (38%) patients across the trial, with the greatest proportion in Arm A (n=8/14, 57%). Additional analysis for this cell subset showed a high PD-1 expression of 68.6% in Arm A at week 27. Furthermore, in 8/15 (53%) Arm A patients with PSA doubling time ≤ 12 months, their median PSA doubling time at Day 0 was 6.2 (range: 2.9- 10.2) months and 19.2 (range: 6.6-100.0) months at week 27. There were 7 Grade 3 adverse events in five patients and no Grade 4-5 adverse events reported. Most adverse events were Grade 1-3 in 82% of patients and the majority of those were associated with injection site reactions.
The authors concluded that the DNA vaccine INO-5150 +/- INO-9012 was safe at the dosages examined. The data demonstrated both PSA and PSMA are immunogenic and INO-5150 induced cellular immune responses. A higher proportion of Arm A patients showed immunological responses as well as improvements in PSA doubling time, specifically patients with PSA doubling time ≤ 12 months, suggesting correlation of immunological efficacy and clinical benefit. Given these initial encouraging results, we eagerly await the planned continued analyses and ongoing follow-up of these patients.
1. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010;363(5):411-422.
Speaker: Neal D. Shore, Atlantic Urology Clinics, Myrtle Beach, United States of America
Co-Authors: E. Heath (Detroit, United States of America) L. Nordquist (Omaha, United States of America) H. Cheng (Seattle, United States of America) K. Bhatt (Plymouth Meeting, United States of America) M. Morrow (Plymouth Meeting, United States of America) T. McMullan (Plymouth Meeting, United States of America) K. Kraynyak (Plymouth Meeting, United States of America) J. Lee (Plymouth Meeting, United States of America) B. Sacchetta (Plymouth Meeting, United States of America) L. Liu (Plymouth Meeting, United States of America) S. Rosencranz (Plymouth Meeting, United States of America) S. T. Tagawa (New York, United States of America) R. A. Parikh (Pittsburg, United States of America) R. Tutrone (Towson, United States of America) J. Garcia (Cleveland, United States of America) Y. Whang (Chapel Hill, United States of America) W. Kelly (Philadelphia, United States of America) I. Csiki (Plymouth Meeting, United States of America) M. Bagarazzi (Plymouth Meeting, United States of America)
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain