Association of putative activated CD8+ T cells with modulation of rising serum PSA levels in biochemically relapsed prostate cancer patients using immunotherapy targeting prostate tumor-associated antigens: a Phase 1 study

Abstract 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 and prostate specific membrane antigen, 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, 2mg INO-5150; B, 8.5mg INO-5150; C, 2mg INO-5150+1mg INO-9012; and D, 8.5 mg INO-5150+1mg INO-9012. Patients received study drug with electroporation on day 0, and weeks 3, 12 and 24, and 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. 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).