A randomized, double-blind, multicenter, phase 2 study of a human monoclonal antibody to human α? integrins (intetumumab) in combination with docetaxel and prednisone for the first-line treatment of patients with metastatic castration-resistant prostate cancer

Intetumumab is a fully human mAb with antiangiogenic, antitumor properties which has shown potential therapeutic effect in castration-resistant prostate cancer (CRPC) patients. In a phase 2, randomized, double-blind, multicenter study, men with metastatic CRPC without prior systemic nonhormonal therapy were randomly assigned to 75-mg/m(2) docetaxel (Taxotere) and 5-mg prednisone plus placebo (N = 65) or 10-mg/kg intetumumab (N = 66) q3w. Placebo patients with progressive disease (PD) could cross over to 10-mg/kg intetumumab alone or with docetaxel. The primary end-point was progression-free survival (PFS). The secondary end-points included tumor response (complete response + partial response, CR + PR), prostate-specific antigen (PSA) response, and overall survival (OS). All efficacy end-points favored placebo over intetumumab, including PFS (median 11.0 versus 7.6 months, P = 0.014), tumor response (20% versus 16%, P = 0.795), PSA response (68% versus 47%, P = 0.018), OS (median 20.6 versus 17.2 months, P = 0.163). Common all-grade adverse events (AEs) with placebo and intetumumab were alopecia (43% versus 26%); diarrhea, leukopenia (both 34% versus 27%); neutropenia (35% versus 23%). Grade >= 3 leukopenia (28% versus 17%) and neutropenia (26% versus 18%) occurred more often with placebo than with intetumumab. Intetumumab serum concentrations increased with repeated dosing and did not reach steady-state. Greater decreases in N-telopeptide of type I collagen (NTx), C-telopeptide (CTx) and CTCs occurred with intetumumab than with placebo. The addition of intetumumab to docetaxel resulted in shorter PFS without additional toxicity among CRPC patients.