国产抗CD20单抗治疗CD20^＋B细胞非霍奇金淋巴瘤的Ⅰ期临床耐受性和药效学研究  

Tolerance and pharmaeodynamics phase Ⅰ clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin＇ s lymphoma

作　　者：姜波 齐军元 孙明媛 李增军 刘薇 刘利军 张凤奎 邱录贵 Jiang Bo;Qi Junyuan;Sun Mingyuan;Li Zengjun;Liu Wei;Liu Lijun;Zhang Fengkui;Qiu Lugui.(Institute of Hematology ＆ Blood Diseases Hospital, CAMS ＆ PUMC, Tianjin 300020, Chin)

机构地区：[1]中国医学科学院、北京协和医学院血液病医院(血液学研究所),天津300020

出　　处：《中华血液学杂志》2018年第4期320-324,共5页Chinese Journal of Hematology

摘　　要：目的通过剂量递增的I期临床试验，评价重组人．鼠嵌合抗CD20单克隆抗体注射液IB1301单次给药在经治疗达客观缓解的CD20^＋B细胞非霍奇金淋巴瘤患者中的耐受性、安全性及药效学特征。方法纳入9例受试者，按剂量递增原则设125、375和500mg／m^2三个剂量组，每组3例逐组完成试验。3组受试者均接受单次IB1301静脉输注，125、375、500mg／m^2组IBl301的中位暴露量分别为243、690、980mg。观察IBI301给药后不良事件（AE）发生情况。采用流式细胞术检测外周血CD19^＋、CD20^＋B细胞比例，采用速率散射比浊法检测血清IgG、IgM水平，进行药效学评价。结果9例受试者发生52例次AE，包括：125mg／m^2组18例次，375mg／m^2组14例次，500mg／m^2组20例次。其中不良反应共26例次，22例次与试验药物可能有关，4例次可能无关；对症处理后均消失或恢复至基线水平。常见的AE包括WBC降低、上呼吸感染、ANC降低、消化不良、高尿酸血症、感觉异常、口腔黏膜炎和头晕。研究中未出现AE导致的用药暂停、受试者退出或试验提前中止，未发生严重AE（SAE）及剂量限制性毒性（DLT）事件。所有受试者CD20^＋、CD19^＋B细胞比例均有不同程度下降，而IgG和IgM水平无明显变化。结论IBI301耐受性良好，受试者出现的不良反应均恢复，未发生SAE及DLT事件。IBI301对CD20^＋B细胞有较好的清除作用。临床试验注册药物临床试验登记与信息公示平台，CTR20140762。Objective To evaluate the tolerance and safety of a human-mouse chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients achieved objective response with CD20^＋ B-cell non-Hodg- kin＇ s lymphoma （NHL）. Methods Nine patients with CD20^＋ B-cell NHL received dose-escalating IBI301 infusions （250 mg/m2, n=3; 375 mg/m2, n=3; 500 mg/m2, n=3, respectively）. The data of all patients were collected for safety analyses. The median exposures of 125 mg/m2, 375 mg/m2, 500 mg/m2 dose groups were 243, 690 and 980 mg, respectively. Safety and tolerability were evaluated by monitoring adverse events （AE）. The ratios of CD19^＋, CD20^＋ B cells and the levels IgG and IgM were detected to evaluate the pharmacodynamics. Results Totally 52 events of AE were observed, including 18 events of AE in 125 mg/m^2 group, 14 events of AE in 375 mg/m^2 group and 20 events of AE in 500 mg/m2 group, respectively. There were 26 adverse reactions of 52 cases of AE, 22 reactions were judged to be probably related to IBI301, and 4 reactions were not probably related to IBI301, all disappeared or returned to baseline levels. Common AE in this study included decreased WBC, upper respiratory infection, decreased neutrophil count, dyspepsia, hyperuricemia, paresthesia, oral mucositis and dizziness. No patients quitted or trial discontinued. No severe AE （SAE） were reported. No dose-limiting toxicity （DLT） events were observed in the study. The ratio of CD20＋ and CD19^＋ B cells decreased in all subjects. There was no significant changes of the levels of IgG and IgM. Conclusions The single dose of IBI301 injection was well tolerated, and the AE occurred in the patients recovered. No SAE were reported, No DLT events were observed in the study. The IBI301 caused an elimination of the peripheral CD20-expressing B cells in all patients. Clinical trial registration Chinadrugtrials. CTR20140762.

关 键 词：嵌合CD20单克隆抗体 非霍奇金淋巴瘤 Ⅰ期临床试验 

分 类 号：R733.1[医药卫生—肿瘤]