A phase I study evaluating cixutumumab, a type 1 insulin-like growth factor receptor inhibitor, given every 2 or 3weeks in Japanese patients with advanced solid tumors.

Abstract

The primary objective of this phase I trial was to establish the safety profile and pharmacokinetics of cixutumumab administered every 2weeks (q2w) or every 3weeks (q3w) in Japanese patients with advanced solid tumors. Exploratory analyses included preliminary antitumor activity. Patients received intravenous cixutumumab q2w or q3w (6-week cycle) in a standard 3+3 study design. Safety was evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Patients received treatment until evidence of progressive disease or other withdrawal criteria were met. Pharmacokinetics were described using noncompartmental analyses. Antitumor activity was evaluated using Response Evaluation Criteria in Solid Tumors v1.0. A total of 21 patients were treated in one of four cohorts: 6mg/kg q2w (n=4); 10mg/kg q2w (n=7); 15mg/kg q3w (n=3); or 20mg/kg q3w (n=7). No patients experienced dose-limiting toxicity. A majority of patients (61.9%) experienced one or more drug-related adverse event (AE). Related AEs included impaired glucose tolerance (n=6 [28.6%]) and diarrhea, nausea, stomatitis, fatigue, weight decrease, anorexia, rash, and hypertension (n=2 each [9.5%]). A best overall response of stable disease was seen in seven patients (33.3%). The median duration of stable disease was 6.9months (range 2.8, 6.9) for all cohorts. Although limited, pharmacokinetic results were as expected and were comparable between Japanese and Caucasian patients. Cixutumumab was generally well tolerated with no new safety concerns. NCT01007032.