Phase 1 studies comparing safety, tolerability, pharmacokinetics and pharmacodynamics of HLX01(a rituximab biosimilar) to reference rituximab in Chinese patients with CD20-positive B-cell lymphoma

查看全文 作　　者：Yuankai [1]Shi;Qingyuan [2]Zhang;Xiaohong [1]Han;Yan [1]Qin;Xiaoyan [3]Ke;Hang [4]Su;Li [5]Liu;Jinxiang [6]Fu;Jie [7]Jin;Jifeng [8]Feng;Xiaonan [9]Hong;Xiaohong [10]Zhang;Depei [11]Wu;Bin [12]Jiang;Xiaodong [13]Dong

机构地区：[1]National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs,Beijing 100021,China;[2]Harbin Medical University Cancer Hospital,Harbin 150081,China;[3]Peking University Third Hospital,Beijing 100191,China;[4]The 307th Hospital of Military Chinese People's Liberation Army,Beijing 100071,China;[5]Tangdu Hospital of the Fourth Military Medical University,Xi'an 710038,China;[6]The Second Affiliated Hospital of Soochow University,Suzhou 215004,China;[7]The First Affiliated Hospital Zhejiang University College of Medicine,Hangzhou 310006,China;[8]Jiangsu Cancer Hospital,Nanjing 210009,China;[9]Fudan University Shanghai Cancer Center,Shanghai 200032,China;[10]The Second Affiliated Hospital Zhejiang University School of Medicine,Hangzhou 310003,China;[11]The First Affiliated Hospital of Soochow University,Suzhou 215006,China;[12]Peking University People's Hospital,Beijing 100034,China;[13]Shanghai Henlius Biotech,Inc.,Shanghai 200233,China

出　　处：《Chinese Journal of Cancer Research》索引2021年第33卷第3期,共12页

基　　金：funded by Shanghai Henlius Biotech, Inc., Science and Technology Commission of Shanghai Municipality (No. 14431908500);China National Major Project for New Drug Innovation (No. 2012ZX09303012)。 摘　　要：Objective: This study aimed to compare the pharmacokinetic, pharmacodynamic and safety profiles of HLX01(a rituximab biosimilar) and reference rituximab sourced from China(Mab Thera?;rituximab-CN).Methods: Here we report the results of two phase 1 studies. In the phase 1 a, open-label, dose-escalation study(NCT03218072, CTR20140400), eligible patients received 250, 375 and 500 mg/m^(2) HLX01 sequentially at 7-day intervals, after confirming no dose-limiting toxicity(DLT). In the phase 1 b, double-blind study(NCT02584920,CTR20140764), eligible patients were given a single dose of 375 mg/m^(2) HLX01 or rituximab-CN. The primary endpoints included safety and tolerability parameters for the phase 1 a and the area under the plasma concentrationtime curve from time zero to day 91(AUC0-91 d) for the phase 1 b study. Equivalence was concluded if 90%confidence interval(90% CI) for the geometric least squares mean ratio(GLSMR) fell in the pre-specified equivalence criteria(80%-125%).Results: Between June 20, 2014 and January 5, 2015, 12 patients were enrolled in the phase 1 a study. The pharmacokinetics of HLX01 showed dose proportionality and accumulation to steady state. HLX01 was well tolerated, with no serious adverse events(AEs), discontinuations or DLTs. Between November 8, 2014 and August13, 2015, 87 eligible patients were enrolled in the phase 1 b study, including 43 who received HLX01 and 44 who were treated with rituximab-CN. The equivalence endpoint was met with GLSMR for AUC0-91 d being 89.6%(90% CI: 80.4%-99.8%). AEs, anti-drug antibodies, and CD19+ and CD20+ B lymphocyte counts were similar between the HLX01 and rituximab-CN treatment groups.Conclusions: Treatment with HLX01 was safe and well tolerated in Chinese patients with B-cell lymphoma.HLX01 and rituximab-CN have similar pharmacokinetic, pharmacodynamic and safety profiles. 关键词：BIOSIMILAR lymphoma monoclonal antibody pharmacokinetics SAFETY

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Phase 1 studies comparing safety, tolerability, pharmacokinetics and pharmacodynamics of HLX01(a rituximab biosimilar) to reference rituximab in Chinese patients with CD20-positive B-cell lymphoma

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