Prospect: A randomized double-blind phase 3 efficacy study of PROSTVAC-VF immunotherapy in men with asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer.

Abstract

TPS5081 Background: PROSTVAC, a targeted active immunotherapy, is being studied in men with asymptomatic to minimally symptomatic mCRPC in PROSPECT, a global double-blind, randomized phase 3 study. PROSTVAC is a prime-boost regimen consisting of subcutaneous administrations of poxvirus-based PROSTVAC-Prime (a modified vaccinia vector) and PROSTVAC–Boost (a modified fowlpox vector) that encode prostate specific antigen (PSA) as the target antigen with three T-cell co-stimulatory molecules (B7.1, ICAM-1, and LFA-3) also known as TRICOM. A statistically significant overall survival (OS) benefit of 8.5 months (P= 0.0061) with a hazard ratio of 0.56 (95% CI, 0.37 to 0.85), and a favorable risk-benefit profile were reported in a randomized, phase 2 study in mCRPC (Kantoff et. al. 2010 J Clin Onc 28:1099-1105). Methods: In PROSPECT, 1200 subjects have been randomized in a double-blind fashion to three arms: PROSTVAC, PROSTVAC plus GM-CSF, or Placebo at a 1:1:1 ratio. The 5 month treatment regimen comprises one PROSTVAC-Prime injection followed by 6 PROSTVAC-Boost injections. Enrolled subjects have asymptomatic/minimally symptomatic mCRPC and are chemotherapy-naïve. Subjects with rapidly progressing disease and visceral metastases are excluded. The primary endpoint is OS and pre-specified interim analyses are integrated in the statistical plan. Secondary efficacy endpoints include the proportion of event-free subjects at 6 months (radiographic progression, pain progression, chemotherapy initiation, or death) compared to placebo. Exploratory endpoints are planned, including immune responses. An immune monitoring program would inform future immunotherapy studies and potential identification of biomarkers. The trial is fully enrolled. ClinicalTrials.gov registry number: NCT01322490. Clinical trial information: NCT01322490.