单位：[1]National Cancer Center/National Clinical Research Center for Cancer/CancerHospital, Beijing Key Laboratory of Clinical Study on Anticancer MolecularTargeted Drugs, Chinese Academy of Medical Sciences & Peking UnionMedical College, Beijing, China[2]Affiliated Cancer Hospital of ZhengzhouUniversity, Henan Cancer Hospital, Zhengzhou, China河南省肿瘤医院[3]Harbin MedicalUniversity Cancer Hospital, Harbin, China[4]Fudan University Shanghai CancerCenter, Shanghai, China[5]Daping Hospital, Third Affiliated Hospital of theArmy Medical University, Chongqing, China[6]The First Bethune Hospital ofJilin University, Changchun, China[7]The Second Hospital of Dalian MedicalUniversity, Dalian, China[8]Jiangsu Cancer Hospital and Jiangsu Institute ofCancer Research, Nanjing, China[9]Changhai Hospital, Shanghai, China[10]Tianjin Medical University Cancer Institute & Hospital, Tianjin, China[11]Cancer Center of Guangzhou Medical University, Guangzhou, China[12]Fujian Provincial Cancer Hospital, Fuzhou, China[13]Fujian Medical UniversityUnion Hospital, Fuzhou, China[14]Beijing Friendship Hospital, Capital MedicalUniversity, Beijing, China首都医科大学附属北京友谊医院[15]The First Affiliated Hospital of SoochowUniversity, Soochow, China[16]The 307th Hospital of Chinese People’sLiberation Army, Beijing, China[17]Tianjin People’s Hospital, Tianjin, China[18]Zhejiang Cancer Hospital, Hangzhou, China浙江省肿瘤医院[19]Shanghai ChangzhengHospital, Shanghai, China[20]The First Affiliated Hospital of ZhengzhouUniversity, Zhengzhou, China[21]The Second Affiliated Hospital of ZhejiangUniversity School of Medicine, Hangzhou, China[22]Jinan Central HospitalAffiliated to Shandong University, Jinan, China[23]Peking University ThirdHospital, Beijing, China[24]Tangdu Hospital, Air Force Medical University, Xi’an,China[25]Hubei Cancer Hospital, Wuhan, China[26]The First Affiliated Hospitalof Nanchang University, Nanchang, China[27]The Second Hospital of JilinUniversity, Changchun, China[28]The First Affiliated Hospital, College ofMedicine, Zhejiang University, Hangzhou, China浙江大学医学院附属第一医院[29]Liaoning Cancer Hospital& Institute, Shenyang, China[30]Guangdong Provincial People’s Hospital,Guangzhou, China[31]Jilin Cancer Hospital, Changchun, China[32]HunanCancer Hospital, Changsha, China[33]Xiangya Hospital, Central SouthUniversity, Changsha, China[34]Shanghai Henlius Biotech, Inc., Shanghai,China
Rituximab in combination with chemotherapy has shown efficacy in patients with diffuse large B-cell lymphoma (DLBCL) for more than 15 years. HLX01 was developed as the rituximab biosimilar following a stepwise approach to demonstrate biosimilarity in analytical, pre-clinical, and clinical investigations to reference rituximab. With demonstrated pharmacokinetic similarity, a phase 3 multi-center, randomized, parallel, double-blind study (HLX01-NHL03) was subsequently conducted to compare efficacy and safety between HLX01 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (H-CHOP) and reference rituximab plus CHOP (R-CHOP) in a total of 407 treatment-naive, CD20-positive DLBCL patients aged 18-80 years. The primary efficacy endpoint was best overall response rate (ORR) within six cycles of treatment in the per-protocol set (PPS). Secondary endpoints included 1-year efficacy outcomes, safety, and immunogenicity profile. The results showed difference in ORRs [H-CHOP 94.1%; R-CHOP 92.8%] between two treatment groups was 1.4% (95% confidence interval [CI], - 3.59 to 6.32, p = 0.608) which falls within the pre-defined equivalence margin of +/- 12%. The safety profile was comparable between the treatment groups, with a similar overall incidence of treatment-emergent adverse events (H-CHOP 99.5%, R-CHOP 99.0%, p = 1.000) and serious adverse events (H-CHOP 34.0%, R-CHOP 32.5%, p = 0.752). This study established bioequivalence in efficacy and safety between HLX01 and reference rituximab. The trial was registered at on 26 August 2015 [#CTR20150583].
基金：
Shanghai Henlius Biotech, Inc.; China National Major Project for New Drug Innovation [2015ZX09501008, 2017ZX09304015]; Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-1-001]
第一作者单位：[1]National Cancer Center/National Clinical Research Center for Cancer/CancerHospital, Beijing Key Laboratory of Clinical Study on Anticancer MolecularTargeted Drugs, Chinese Academy of Medical Sciences & Peking UnionMedical College, Beijing, China
通讯作者：
推荐引用方式(GB/T 7714)：
Yuankai Shi,Yongping Song,Yan Qin,et al.A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma[J].JOURNAL of HEMATOLOGY & ONCOLOGY.2020,13(1):doi:10.1186/s13045-020-00871-9.
APA：
Yuankai Shi,Yongping Song,Yan Qin,Qingyuan Zhang,Xiaohong Han...&Xin Zhang.(2020).A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma.JOURNAL of HEMATOLOGY & ONCOLOGY,13,(1)
MLA：
Yuankai Shi,et al."A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma".JOURNAL of HEMATOLOGY & ONCOLOGY 13..1(2020)
医学