Icrucumab, a fully human monoclonal antibody against the vascular endothelial growth factor receptor-1, in the treatment of patients with advanced solid malignancies: a Phase 1 study.

BACKGROUND: IMC-18F1 (icrucumab), a human monoclonal antibody against vascular endothelial growth factor receptor-1 (VEGFR-1), potently inhibits ligand-dependent phosphorylation of VEGFR-1 and downstream signaling, making icrucumab an attractive candidate for antitumor activity.
OBJECTIVES: The primary objective was to determine the safety profile and maximum tolerated dose of icrucumab in patients with advanced solid tumors that were previously unresponsive to standard therapy or for which no standard therapy was available.
METHODS: In this open-label, dose-escalation, Phase 1 study, patients received icrucumab intravenously weekly at 2, 3, 6, and 12 mg/kg (Cohorts 1-4), every other week (q2w) at 15 mg/kg (Cohort 5), or every third week at 20 mg/kg (Cohort 6). Patients received icrucumab until evidence of progressive disease or other withdrawal criteria were met.
RESULTS: Twenty-six patients received icrucumab. The most common adverse events were fatigue, nausea, peripheral edema, anemia, dyspnea, and vomiting. No dose-limiting toxicities (DLTs) were observed in Cohorts 1-5. Two DLTs were observed in Cohort 6 (anemia and hyponatremia), and enrollment was stopped. No patient demonstrated an immunogenic response. Overall, icrucumab exhibited nonlinear pharmacokinetics at doses >6 mg/kg. Six patients (23.1 %) achieved stable disease with median duration of 11.1 weeks (range = 10.3-18.7 weeks); tumor types were thyroid, melanoma, colorectal (3 patients), and small-cell lung cancers.
CONCLUSIONS: Icrucumab was safely administered weekly at doses of 2-12 mg/kg and q2w at a dose of 15 mg/kg with no DLTs. Based on achievement of stable disease, icrucumab has potential for antitumor activity against advanced solid tumors.