Clinical Trial

. 2021 Apr;38(4):1889-1903.

doi: 10.1007/s12325-020-01603-8. Epub 2021 Mar 9.

Efficacy and Safety of the Biosimilar IBI301 Plus Standard CHOP (I-CHOP) in Comparison With Rituximab Plus CHOP (R-CHOP) in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL): A Randomized, Double-Blind, Parallel-Group, Phase 3 Trial

Yuqin Song¹, Hui Zhou², Huilai Zhang³, Wei Liu⁴, Yuerong Shuang⁵, Keshu Zhou⁶, Fangfang Lv⁷, Hao Xu⁸, Jianfeng Zhou⁹, Wei Li¹⁰, Huaqing Wang¹¹, Hongyu Zhang¹², Haiwen Huang¹³, Qingyuan Zhang¹⁴, Wei Xu¹⁵, Zheng Ge¹⁶, Ying Xiang¹⁷, Shuye Wang¹⁸, Da Gao¹⁹, Shun'e Yang²⁰, Jinying Lin²¹, Lin Wang²², Liqun Zou²³, Meifang Zheng²⁴, Jing Liu²⁵, Zonghong Shao²⁶, Ying Pang²⁷, Ruixiang Xia²⁸, Zhendong Chen²⁹, Ming Hou³⁰, Hongxia Yao³¹, Ru Feng³², Zhen Cai³³, Mingzhi Zhang³⁴, Wenhua Ran³⁵, Lin Liu³⁶, Shan Zeng³⁷, Wei Yang³⁸, Peng Liu³⁹, Aibin Liang⁴⁰, Xuelan Zuo⁴¹, Qingfeng Zou⁴², Junxun Ma⁴³, Wei Sang⁴⁴, Ye Guo⁴⁵, Wei Zhang⁴⁶, Yongqing Cao⁴⁷, Yan Li⁴⁸, Jifeng Feng⁴⁹, Xin Du⁵⁰, Xiaohong Zhang⁵¹, Hongguo Zhao⁵², Hui Zhou⁵³, Jie Yu⁵³, Xing Sun⁵³, Jun Zhu⁵⁴, Lugui Qiu⁵⁵

Affiliations

¹ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital and Institute, Beijing, China.
² Department of Lymphoma and Hematology, Hunan Province Cancer Hospital, Changsha, China.
³ Department of Lymphoma, Tianjin Cancer Hospital, Tianjin, China.
⁴ State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
⁵ Cancer Chemotherapy Center, Jiangxi Province Cancer Hospital, Nanchang, China.
⁶ Hematology Department, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
⁷ Oncology Department, Fudan University Cancer Hospital, Shanghai, China.
⁸ Hematology Department, Yancheng City No. 1 People's Hospital, Yancheng, China.
⁹ Hematology Department, Tongji Medical College Huazhong University of Science and Technology, Wuhan, China.
¹⁰ Hematology Department, The First Hospital of Jilin University, Changchun, China.
¹¹ Oncology Department, Tianjin City People's Hospital, Tianjin, China.
¹² Oncology Department, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, China.
¹³ Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
¹⁴ Department of Oncology, Affiliated Cancer Hospital of Harbin Medical University, Harbin, China.
¹⁵ Hematology Department, Jiangsu Province Hospital, Nanjing, China.
¹⁶ Hematology Department, Zhongda Hospital Southeast, Nanjing, China.
¹⁷ Department of Hematology and Oncology, Chongqing Cancer Hospital, Chongqing, China.
¹⁸ Hematology Department, First Affiliated Hospital of Harbin Medical University, Harbin, China.
¹⁹ Hematology Department, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
²⁰ Department of Lymphoma and Breast Cancer, First Affiliated Hospital of Xinjiang Medical University, Urumchi, China.
²¹ Department of Hematological Rheumatology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
²² Oncology Department, Hainan General Hospital, Haikou, China.
²³ Department of Oncology, West China Hospital Sichuan University, Chengdu, China.
²⁴ Department of Hematology, Linyi Cancer Hospital, Linyi, China.
²⁵ Hematology Department, Third Xiangya Hospital of Central South University, Changsha, China.
²⁶ Hematology Department, General Hospital, Tianjin Medical University, Tianjin, China.
²⁷ Hematology Department, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
²⁸ Hematology Department, First Affiliated Hospital of Anhui Medical University, Hefei, China.
²⁹ Oncology Department, Second Affiliated Hospital of Anhui Medical University, Hefei, China.
³⁰ Hematology Department, Qilu Hospital of Shandong University, Jinan, China.
³¹ Hematology Department, Hainan General Hospital, Haikou, China.
³² Hematology Department, Nanfang Hospital, Guangzhou, China.
³³ Department of Hematology, First Affiliated Hospital of Zhejiang Medical University, Hangzhou, China.
³⁴ Oncology Department, First Affiliated Hospital of Zhengzhou Medical University, Zhengzhou, China.
³⁵ Cancer Center, Chongqing Three-Gorge Central Hospital, Chongqing, China.
³⁶ Hematology Department, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
³⁷ Oncology Department, Xiangya Hospital Central South University, Changsha, China.
³⁸ Hematology Department, Shengjing Hospital of China Medical University, Shenyang, China.
³⁹ Hematology Department, Affiliated Zhongshan Hospital of Fudan University, Shanghai, China.
⁴⁰ Hematology Department, Tongji Hospital of Tongji University, Shanghai, China.
⁴¹ Hematology Department, Zhongnan Hospital of Wuhan, Wuhan, China.
⁴² Department of Oncology, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.
⁴³ Department of Oncology, Chinese PLA General Hospital, Beijing, China.
⁴⁴ Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
⁴⁵ Oncology Department, Shanghai East Hospital, Shanghai, China.
⁴⁶ Hematology Department, Peking Union Medical College Hospital, Beijing, China.
⁴⁷ Department of Hematology and Oncology, First Hospital of Changsha, Changsha, China.
⁴⁸ Hematology Department, First Affiliated Hospital of China Medical University, Shenyang, China.
⁴⁹ Oncology Department, Jiangsu Cancer Hospital, Nanjing, China.
⁵⁰ Hematology Department, Second People's Hospital of Shenzhen, Shenzhen, China.
⁵¹ Hematology Department, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
⁵² Hematology Department, Affiliated Hospital of Qingdao University, Qingdao, China.
⁵³ Innovent Biologics, Inc, Suzhou, China.
⁵⁴ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital and Institute, Beijing, China. zhu-jun2017@outlook.com.
⁵⁵ State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. qiulg@ihcams.ac.cn.

PMID: 33751401
DOI: 10.1007/s12325-020-01603-8

Clinical Trial

Efficacy and Safety of the Biosimilar IBI301 Plus Standard CHOP (I-CHOP) in Comparison With Rituximab Plus CHOP (R-CHOP) in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL): A Randomized, Double-Blind, Parallel-Group, Phase 3 Trial

Yuqin Song et al. Adv Ther. 2021 Apr.

. 2021 Apr;38(4):1889-1903.

doi: 10.1007/s12325-020-01603-8. Epub 2021 Mar 9.

Authors

Affiliations

¹ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital and Institute, Beijing, China.
² Department of Lymphoma and Hematology, Hunan Province Cancer Hospital, Changsha, China.
³ Department of Lymphoma, Tianjin Cancer Hospital, Tianjin, China.
⁴ State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
⁵ Cancer Chemotherapy Center, Jiangxi Province Cancer Hospital, Nanchang, China.
⁶ Hematology Department, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
⁷ Oncology Department, Fudan University Cancer Hospital, Shanghai, China.
⁸ Hematology Department, Yancheng City No. 1 People's Hospital, Yancheng, China.
⁹ Hematology Department, Tongji Medical College Huazhong University of Science and Technology, Wuhan, China.
¹⁰ Hematology Department, The First Hospital of Jilin University, Changchun, China.
¹¹ Oncology Department, Tianjin City People's Hospital, Tianjin, China.
¹² Oncology Department, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, China.
¹³ Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
¹⁴ Department of Oncology, Affiliated Cancer Hospital of Harbin Medical University, Harbin, China.
¹⁵ Hematology Department, Jiangsu Province Hospital, Nanjing, China.
¹⁶ Hematology Department, Zhongda Hospital Southeast, Nanjing, China.
¹⁷ Department of Hematology and Oncology, Chongqing Cancer Hospital, Chongqing, China.
¹⁸ Hematology Department, First Affiliated Hospital of Harbin Medical University, Harbin, China.
¹⁹ Hematology Department, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
²⁰ Department of Lymphoma and Breast Cancer, First Affiliated Hospital of Xinjiang Medical University, Urumchi, China.
²¹ Department of Hematological Rheumatology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
²² Oncology Department, Hainan General Hospital, Haikou, China.
²³ Department of Oncology, West China Hospital Sichuan University, Chengdu, China.
²⁴ Department of Hematology, Linyi Cancer Hospital, Linyi, China.
²⁵ Hematology Department, Third Xiangya Hospital of Central South University, Changsha, China.
²⁶ Hematology Department, General Hospital, Tianjin Medical University, Tianjin, China.
²⁷ Hematology Department, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
²⁸ Hematology Department, First Affiliated Hospital of Anhui Medical University, Hefei, China.
²⁹ Oncology Department, Second Affiliated Hospital of Anhui Medical University, Hefei, China.
³⁰ Hematology Department, Qilu Hospital of Shandong University, Jinan, China.
³¹ Hematology Department, Hainan General Hospital, Haikou, China.
³² Hematology Department, Nanfang Hospital, Guangzhou, China.
³³ Department of Hematology, First Affiliated Hospital of Zhejiang Medical University, Hangzhou, China.
³⁴ Oncology Department, First Affiliated Hospital of Zhengzhou Medical University, Zhengzhou, China.
³⁵ Cancer Center, Chongqing Three-Gorge Central Hospital, Chongqing, China.
³⁶ Hematology Department, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
³⁷ Oncology Department, Xiangya Hospital Central South University, Changsha, China.
³⁸ Hematology Department, Shengjing Hospital of China Medical University, Shenyang, China.
³⁹ Hematology Department, Affiliated Zhongshan Hospital of Fudan University, Shanghai, China.
⁴⁰ Hematology Department, Tongji Hospital of Tongji University, Shanghai, China.
⁴¹ Hematology Department, Zhongnan Hospital of Wuhan, Wuhan, China.
⁴² Department of Oncology, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.
⁴³ Department of Oncology, Chinese PLA General Hospital, Beijing, China.
⁴⁴ Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
⁴⁵ Oncology Department, Shanghai East Hospital, Shanghai, China.
⁴⁶ Hematology Department, Peking Union Medical College Hospital, Beijing, China.
⁴⁷ Department of Hematology and Oncology, First Hospital of Changsha, Changsha, China.
⁴⁸ Hematology Department, First Affiliated Hospital of China Medical University, Shenyang, China.
⁴⁹ Oncology Department, Jiangsu Cancer Hospital, Nanjing, China.
⁵⁰ Hematology Department, Second People's Hospital of Shenzhen, Shenzhen, China.
⁵¹ Hematology Department, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
⁵² Hematology Department, Affiliated Hospital of Qingdao University, Qingdao, China.
⁵³ Innovent Biologics, Inc, Suzhou, China.
⁵⁴ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital and Institute, Beijing, China. zhu-jun2017@outlook.com.
⁵⁵ State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. qiulg@ihcams.ac.cn.

PMID: 33751401
DOI: 10.1007/s12325-020-01603-8

Abstract

Introduction: Patients with diffuse large B-cell lymphoma (DLBCL) have limited access to rituximab. IBI301 is a recombinant chimeric murine/human anti-CD20 monoclonal antibody and is a candidate biosimilar to rituximab. This study aimed to assess the therapeutic equivalence of IBI301 and rituximab in previously untreated patients with diffuse large B-cell lymphoma (DLBCL).

Methods: This multicenter, randomized, double-blind, parallel-group, phase 3 trial compared IBI301 and rituximab, both plus the chemotherapy of doxorubicin, cyclophosphamide, vindesine, and prednisone (CHOP), was conducted in 68 centers across China. Eligible patients with untreated CD20 positive (CD20⁺) DLBCL randomly received IBI301 (375 mg/m²) plus the standard CHOP or rituximab (375 mg/m²) plus the standard CHOP for six cycles of a 21-day cycle. The primary end point was the overall remission rate (ORR). Efficacy equivalence was defined if 95% CIs for the ORR difference between the two groups were within a ± 12.0% margin.

Results: Between August 22, 2016, and September 5, 2018, 419 patients were randomly allocated into the IBI301 group (N = 209) and rituximab group (N = 210). In the full analysis set, the ORR was 89.9% and 93.8% in the IBI301 and rituximab groups, respectively, and the ORR difference was -3.9% (95% CI - 9.1%-1.3%), falling within a ± 12.0% margin. The occurrences of treatment-emergent adverse events (TEAEs) (100% vs. 99.0%) and AEs of grade ≥ 3 (87.1% vs. 83.3%) were similar in the two groups (P > 0.05).

Conclusions: IBI301 had a non-inferiority efficacy and a comparable safety compared with rituximab. IBI301 plus CHOP could be suggested as a candidate treatment regimen for untreated patients with CD20⁺ DLBCL.

Trial registration: This trial is registered on ClinicalTrials.gov (NCT02867566).

Keywords: Biosimilar; CHOP; DLBCL; IBI301; Rituximab.

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Efficacy and Safety of the Biosimilar IBI301 Plus Standard CHOP (I-CHOP) in Comparison With Rituximab Plus CHOP (R-CHOP) in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL): A Randomized, Double-Blind, Parallel-Group, Phase 3 Trial

Affiliations

Efficacy and Safety of the Biosimilar IBI301 Plus Standard CHOP (I-CHOP) in Comparison With Rituximab Plus CHOP (R-CHOP) in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL): A Randomized, Double-Blind, Parallel-Group, Phase 3 Trial

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