The management of men with prostate cancer (PCa) with biochemical recurrence following local definitive therapy remains controversial. Early use of androgen deprivation therapy (ADT) leads to significant side effects. Developing an alternative, clinically effective, and well-tolerated therapy remains an unmet clinical need. INO-5150 is a synthetic DNA therapy that includes plasmids encoding for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA), and INO-9012 is a synthetic DNA plasmid encoding for interleukin-12 (IL-12). This phase 1/2, open-label, multi-center study enrolled men with PCa with rising PSA after surgery and/or radiation therapy. Patients were enrolled into one of four treatment arms: arm A, 2 mg of INO-5150; arm B, 8.5 mg of INO-5150; arm C, 2 mg of INO-5150 + 1 mg of INO-9012; and arm D, 8.5 mg of INO-5150 + 1 mg of INO-9012. Patients received study drug with electroporation on day 0 and on weeks 3, 12, and 24, and they were followed for up to 72 weeks. Sixty-two patients were enrolled. Treatment was well tolerated. 81% (50/62) of patients completed all visits. 85% (53/62) remained progression-free at 72 weeks. PSA doubling time (PSADT) was increased when assessed in patients with day 0 PSADT ≤12 months. Immunogenicity was observed in 76% (47/62) of patients by multiple assessments. Analysis indicated that CD38 and perforin co-positive CD8 T cell frequency correlated with attenuated PSA rise (p = 0.05, n = 50).
Molecular therapy : the journal of the American Society of Gene Therapy. 2020 Mar 03 [Epub ahead of print]
Neal D Shore, Matthew P Morrow, Trevor McMullan, Kimberly A Kraynyak, Albert Sylvester, Khamal Bhatt, Jocelyn Cheung, Jean D Boyer, Li Liu, Brian Sacchetta, Samantha Rosencranz, Elizabeth I Heath, Luke Nordquist, Heather H Cheng, Scott T Tagawa, Leonard J Appleman, Ronald Tutrone, Jorge A Garcia, Young E Whang, W Kevin Kelly, David B Weiner, Mark L Bagarazzi, Jeffrey M Skolnik
Carolina Urologic Research Center, Myrtle Beach, SC, USA., Inovio Pharmaceuticals, Plymouth Meeting, PA, USA. Electronic address: ., Inovio Pharmaceuticals, Plymouth Meeting, PA, USA., Karmanos Cancer Institute, Detroit, MI, USA., GU Research Network LLC/Urology Cancer Center, Omaha, NE, USA., University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Weill Cornell Medical College, New York, NY, USA., University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Greater Baltimore Medical Center (GBMC), Chesapeake Urology Associates (CUA), Towson, MD, USA., Cleveland Clinic, Cleveland, OH, USA., Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Thomas Jefferson University, Philadelphia, PA, USA., The Wistar Institute, Philadelphia, PA, USA.