Ipilimumab (IPI) in metastatic castrate-resistant prostate cancer (mCRPC): Results from an open-label, multicenter phase I/II study.

25 Background: IPI is a fully human, anti-CTLA-4 monoclonal antibody capable of enhancing anti-tumor immunity. Preclinically, radiotherapy (XRT) and CTLA-4 blockade have synergistic anti-tumor activity. This phase 1/2 study in patients (pts) with mCRPC was designed to assess: safety of IPI at various doses, feasibility of combining IPI with XRT, and activity. Methods: mCRPC pts with or without prior chemotherapy were enrolled. In the dose-escalation phase, 33 pts (³6 pts per cohort) received IPI q3 weeks x 4 doses at 3, 5, or 10 mg/kg, or with XRT at 3 or 10 mg/kg. Single dose XRT (8 Gy/lesion, up to 3 lesions per pt) was given 24 to 48 h before the first IPI dose. The 10 mg/kg ± XRT cohorts were expanded to 50; 34 received IPI + XRT (Table). Based on clinical benefit, pts received additional doses of IPI. Endpoints were safety, and activity as assessed by serum prostate-specific antigen (PSA) and RECIST criteria. PSA was monitored monthly, with scans q3 months (mos). Results: There were no dose-limiting ...