A phase 1, multicenter, open-label study of the safety of two dose levels of a human monoclonal antibody to human α_v integrins, intetumumab, in combination with docetaxel and prednisone in patients with castrate-resistant metastatic prostate cancer

Purpose: We evaluated the safety and efficacy of intetumumab in combination with docetaxel in patients with castrate-resistant metastatic prostate cancer. Patients and methods: In this phase 1, open-label, multicenter, nonrandomized study, 75 mg/m² docetaxel was administered on Day 1 of each of nine 21-day treatment cycles and intetumumab 5 or 10 mg/kg was administered on Days 1, 8, and 15 of Cycles 2 and 3 and on Day 1 of all subsequent cycles. The primary endpoint was the incidence of dose-limiting toxicities (DLTs) during Cycles 2 and 3. Secondary endpoints included serum prostate-specific antigen (PSA) response and objective response based on Response Evaluation Criteria in Solid Tumors (RECIST). Results: Ten patients were treated (5 mg/kg n=3, 10 mg/kg n=7). No DLTs occurred. Most treatment-emergent adverse events (TEAEs) occurred in the 10-mg/kg intetumumab group. Common TEAEs were neutropenia (10 mg/kg n=6) and nausea (5 mg/kg n=1, 10 mg/kg n=5). Four 10-mg/kg-treated patients reported serious TEAEs; of these, only febrile neutropenia was considered probably intetumumab-related. In the 10-mg/kg group, four patients had a serum PSA response (two of whom responded within 3 months of treatment), one patient demonstrated partial tumor response for 11 weeks, and none had progressive disease at Cycle 9. No PSA or tumor response was observed in the 5-mg/kg group. Conclusions: Intetumumab was generally safe and well tolerated in combination with docetaxel, with a higher incidence of TEAEs in the 10 mg/kg dose cohort. The efficacy of 10 mg/kg intetumumab in combination with docetaxel appears to warrant further study.