Figitumumab in patients with refractory metastatic colorectal cancer previously treated with standard therapies: a nonrandomized, open-label, phase II trial.

Purpose: Figitumumab (CP-751,871) is a human IgG2 monoclonal antibody that binds and down-regulates insulin-like growth factor receptor-1 (IGF-1R) and inhibits activation of this receptor by IGF-1 and IGF-2. This nonrandomized, open-label, single-arm, phase II trial evaluated the antitumor activity and safety of figitumumab in patients with metastatic colorectal cancer that was refractory to ≥2 systemic therapies. Methods: Cohorts A and B received intravenous figitumumab 20 and 30 mg/kg in 3-week cycles, respectively. Both received loading doses (20 or 30 mg/kg) on days 1 and 2 of cycle 1. The primary endpoint was 6-month survival (null hypothesis for each cohort, H: p = 0.45). Secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response, safety, and pharmacokinetics. Results: A total of 168 patients (Cohort A, n = 85; Cohort B, n = 83) received figitumumab. Estimated 6-month survival was 49.4 % (95 % CI 38.8-60.0) in Cohort A and 44.1 % (95 % CI 33.4-54.9) in Cohort B. Median OS was 5.8 and 5.6 months, respectively; median PFS was 1.4 months in both cohorts. No objective partial or complete responses occurred. The respective rates of treatment discontinuation due to treatment-related adverse events (AEs) were 5 and 7 %. The most common grade 3/4 nonhematologic AEs in both cohorts were hyperglycemia and asthenia. No grade 4 hematologic laboratory abnormalities occurred. Most deaths were reported as due to progressive disease; none were due to figitumumab. Conclusion: Six-month survival data do not support further study of figitumumab 20 or 30 mg/kg in this patient population. [ABSTRACT FROM AUTHOR]