重组抗表皮生长因子受体人鼠嵌合单克隆抗体治疗晚期恶性肿瘤Ⅰ期临床试验

目的 评价重组抗表皮生长因子受体(EGFR)人鼠嵌合单克隆抗体(CMAB009)在晚期肿瘤患者中的药代动力学特点和安全性,初步观察疗效.方法 单中心、开放的Ⅰ期临床试验.试验分单次和多次给药两阶段.单次给药设100、250、400mg/m2三个剂量组,随后的多次给药分两组,A组为250 mg/m2,每周一次,连用4周;B组起始剂量400mg/m2,以后每周250 mg/m2,连用4周.多次给药后部分缓解(PR)或稳定(SD)的患者,继续每周给药250 mg/m2,直至病情进展或无法耐受.结果 2008年1～8月,共入组18例受试者,均来自中国医学科学院肿瘤医院.其中结直肠癌10例,非小细胞肺癌7例,胃癌1例.未观察到3/4级不良反应.1/2级不良反应主要有皮疹、甲沟炎、发热、恶心和头痛.2例(13.3%)结直肠癌患者获得PR,至疾病进展时间(TTP)分别为24和16周.结论 CMAB009的耐受性良好,不良反应均为1～2级,最常见的不良反应为皮疹和甲沟炎,可以观察到抗肿瘤疗效.

Abstract：

Objective To characterize the safety profiles and serum pharmacokinetic effects of antiepidermal 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/m2) 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/m2, group B with the initial dose of 400 mg/m2, followed by 3 weekly doses of 250 mg/m2. 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.

Phase Ⅰ study of anti-EGFR monoclonal antibody (CMAB009) in patients with advanced cancer

Objective To characterize the safety profiles and serum pharmacokinetic effects of antiepidermal 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/m2) 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/m2, group B with the initial dose of 400 mg/m2, followed by 3 weekly doses of 250 mg/m2. 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.