CA184-043: A randomized, double-blind, phase III trial comparing ipilimumab versus placebo following a single dose of radiotherapy (RT) in patients (pts) with castration-resistant prostate cancer (CRPC) who have received prior treatment with docetaxel (D).

TPS4689 Background: Ipilimumab (Ipi), a fully human monoclonal antibody which blocks CTLA-4, augments antitumor immune responses. Ipi has shown antitumor effects in prostate cancer model systems and clinical activity (via prostate-specific antigen [PSA] declines and RECIST response) in Phase 1/2 investigations in CRPC, with a side effect profile reflective of its mechanism of action. Preclinical data suggest that RT given prior to CTLA-4 blockade may increase antitumor activity. Methods: In this study, pts with CRPC who have progressed during or after D are randomized 1:1 to receive either a single dose of bone-directed RT followed by Ipi 10mg/kg, or RT followed by placebo. Within 2 days of RT administration (up to 5 lesions at 8 Gy on a single day) patients receive their initial dose of Ipi/placebo; Ipi/placebo is then given every 3 weeks for a total of 4 doses. Eligible pts may continue to receive blinded study drug every 12 weeks until they meet treatment stopping criteria, withdraw consent, are lost to follow-up, or study closure. The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival, pain response, and safety. The study is designed to detect a 3.8 month difference (HR=0.76) in median OS with 90% power and 0.05 2-sided type one error. The enrollment goal is 800 randomized patients, with a single interim analysis for superiority of OS planned at 435 events at approximately 33 months from first patient first visit (ClinicalTrials.gov identifier: NCT00861614). [Table: see text] [Table: see text]