Cetuximab biosimilar (Zhangjiang Biotech)

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.

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.

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.

As a well-tolerated antitumor agent, CMAB009 may be safely administered by the above multi-dosing protocol.

In the present study, we conducted a Phase 1 study of a recombinant anti-EGFR monoclonal antibody (CMAB009) that has the same amino acid sequence as cetuximab. The purpose of this study was to evaluate the safety, pharmacokinetics, and potential benefit of CMAB009 in Chinese patients with advanced chemotherapy-resistant epithelial malignancies. In this study, 18 patients were treated with two successive treatment schedules comprising a single-dose escalation phase followed by a weekly, multiple-dose extension phase. No dose-limiting toxicity was reported during the evaluation period. CMAB009-associated toxicity was minimal, and the most commonly reported adverse events were fever, asthenia, transaminase elevation, nausea, and skin toxicities. CMAB009 exhibited a non-linear PK profile over the dose range of 100 to 400 mg/m2. In the single-dose phase, CMAB009 reached peak serum concentrations at the end of the infusion and then declined slowly with a Tl/2 of 77.15 ±13.96 h, 79.79 ±6.91 h, and 86.25 ±9.93 h after infusion of 100, 250, and 400 mg/m ( 2) based on a two compartmental model analysis. Mean Cmax increased roughly dose-proportional while AUC0-∞ showed a greater than dose-proportionate increase from 100 to 400 mg/m ( 2) . After multiple infusions, serum concentrations dropped slowly and the Tl/2 was 102.25 ± 33.54 h and 118.91 ± 29.12 h based on a two compartmental model analysis. No neutralizing anti-antibody antibodies were detectable. Two patients achieved partial remissions. The study results suggest that CMAB009 shows acceptable tolerance and primary efficacy and should be studied as a treatment in patients with advanced chemotherapy-resistant epithelial malignancies.