Phase II trial of figitumumab in patients with refractory, metastatic colorectal cancer (mCRC).

3525 Background: Figitumumab (F; CP-751,871) is a fully human monoclonal antibody (mAb) that inhibits IGF-IR. This phase II trial examined the efficacy and safety of F in patients (pts) with refractory mCRC. METHODS: Pts (male or female) had an ECOG PS of 0 or 1, and had received prior chemotherapy (+/- mAb therapy). Cohort A received intravenous (iv) F 20 mg/kg q3w. Following a protocol amendment a further cohort received iv F 30 mg/kg q3w (Cohort B). F was dosed on days 1 and 2 of cycle 1 (loading dose) and on day 1 of each subsequent cycle. The primary endpoint was 6-month overall survival (6-mo OS). HYPOTHESIS: H0 p=.45 (p=probability of 6-mo OS) vs. H1 p>.45. Secondary endpoints included safety, PFS, OS, and PK. Associations between plasma levels of free-IGF-1 (fIGF-1) and OS were examined. RESULTS: 168 pts (Cohort A n=85; Cohort B n=83) were treated. Pts were heavily pretreated: 76% (Cohort A) and 77% (Cohort B) had received ≥3 prior systemic regimes. The probability of 6-mo OS was not significantly greater than .45 for either cohort (Table). There was a trend toward longer median OS in pts with high levels of fIGF-1 (Table). The most common grade 3/4 non-hematologic AEs in Cohort A were hyperglycemia (16%), asthenia (13%), and fatigue (6%), and in Cohort B hyperglycemia (22%) and asthenia (13%). The most common hematologic abnormalities in both cohorts were lymphopenia (Cohort A 6%; Cohort B 4%) and anemia (Cohort A 5%; Cohort B 3%). Overall, F 20 mg/kg was better tolerated than F 30 mg/kg. Plasma concentrations of F suggest that a loading dose of F facilitated early achievement of steady state concentrations in Cycle 1. CONCLUSIONS: 6-mo OS results do not support further study of F 20 or 30 mg/kg in pts with refractory mCRC. In both cohorts there was a trend toward longer median OS in pts with high levels of fIGF-1. [Table: see text].