Objective: To characterize the safety profiles and serum pharmacokinetic effects of anti-epidermal growth factor receptor monoclonal antibody (CMAB009) in advanced cancer patients and evaluate the preliminary evidence of its anti-tumor activity.
Methods: This phase I, single-center clinical trial had 2 phases of treatment: single-dose phase, followed by a fixed weekly dose. Subjects meeting the inclusion criteria were enrolled. The subjects were randomly assigned to receive 1 of 3 initial doses of CMAB009 (100, 250 & 400 mg/m(2)) for the purpose of single-dose pharmacokinetic evaluation. After a 28-day washout period of allowing for the characterization of pharmacokinetic end points, the eligible patients were permitted to undergo a successive multi-dose phase study. They were divided into 2 dose groups, group A with 4 weekly doses of 250 mg/m(2), group B with the initial dose of 400 mg/m(2), followed by 3 weekly doses of 250 mg/m(2). The subjects were closely monitored for adverse events throughout the trial.
Results: A total of 18 subjects were recruited, including colorectal cancer (n = 10), non-small cell lung cancer (n = 7) and gastric cancer (n = 1). CMAB009-associated toxicity was minimal. And the most commonly reported Grade 1/2 adverse events were skin rashes, fever, nausea and headache. Two patients with colorectal cancer achieved partial remission and the time to progression (TTP) was 24 and 16 weeks respectively.
Conclusion: As a well-tolerated antitumor agent, CMAB009 may be safely administered by the above multi-dosing protocol.