Gagnier, Paul

TPS5093 Background: Globally, docetaxel remains the standard of care for metastatic CRPC; however, its use may be delayed until pts develop symptoms. The presence of infiltrating leukocytes in CRPC tumors suggests a natural antitumor immune response is occurring. This is supported by an overall survival (OS) benefit reported in men with asymptomatic or minimally symptomatic metastatic CRPC who received sipuleucel-T. Ipi, a monoclonal antibody that binds CTLA-4, augments antitumoral activity of cytotoxic immune cells. Ipi demonstrated OS benefit in two phase III trials for advanced melanoma, with side effects that were managed using product-specific treatment guidelines. In phase I/II trials in metastatic CRPC, Ipi has shown clinical activity (as measured by prostate-specific antigen [PSA] declines and RECIST response) with a similar toxicity profile to that observed in melanoma. This global (149 sites in 24 countries) phase III study (ClinicalTrials.gov identifier: NCT01057810) evaluates Ipi vs placebo in chemotherapy-naïve pts with asymptomatic or minimally symptomatic CRPC without visceral metastases. Methods: The primary endpoint is OS; secondary endpoints include progression-free survival, time to pain progression, time to non-hormonal systemic therapy and safety characterization. The study is designed to detect a 9.3-month median difference (HR=0.7) in OS with 90% power and 0.05 two-sided significance. Pts are randomized at a 2:1 ratio to receive Ipi 10 mg/kg every 3 weeks for up to 4 doses or placebo as induction therapy. Eligible pts will receive maintenance therapy of blinded study drug every 12 weeks. The accrual goal is 600 pts randomized. Clinical trial information: NCT01057810. [Table: see text] [Table: see text]