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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

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).

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Acknowledgements

The authors are grateful to all the patients participating in this trial, and all their families. They also thank the investigators and staff.

Funding

This study was funded by Innovent Biologics and co-funded by Eli Lilly and Company. The sponsors also funded the journal’s Rapid Service fee.

Medical Writing Assistance

We thank the editorial staff of Innovent Biologics, Inc. (the study sponsor), Xia Yin, for providing writing support.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosures

Hui Zhou (Innovent), Jie Yu, and Xing Sun are employees of Innovent Biologics, Inc. Yuqin Song, Hui Zhou, Huilai Zhang, Wei Liu, Yuerong Shuang, Keshu Zhou, Fangfang Lv, Hao Xu, Jianfeng Zhou, Wei Li, Huaqing Wang, Hongyu Zhang, Haiwen Huang, Qingyuan Zhang, Wei Xu, Zheng Ge, Ying Xiang, Shuye Wang, Da Gao, Shun’e Yang, Jinying Lin, Lin Wang, Liqun Zou, Meifang Zheng, Jing Liu, Zonghong Shao, Ying Pang, Ruixiang Xia, Zhendong Chen, Ming Hou, Hongxia Yao, Ru Feng, Zhen Cai, Mingzhi Zhang, Wenhua Ran, Lin Liu, Shan Zeng, Wei Yang, Peng Liu, Aibin Liang, XuelanZuo, Qingfeng Zou, Junxun Ma, Wei Sang, Ye Guo, Wei Zhang, Yongqing Cao, Yan Li, Jifeng Feng, Xin Du, Xiaohong Zhang, Hongguo Zhao, Hui Zhou, Jun Zhu, and Lugui Qiu have nothing to disclose.

Compliance with Ethics Guidelines

The study was approved by the ethics committee of the Institute of Hematology and Blood Diseases Hospital and the ethics committee at each center. This study was performed in accordance with the guidance on the ethical principles of the Declaration of Helsinki and the Good Clinical Practice (GCP). Written informed consent was obtained from all patients.

Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Correspondence to Jun Zhu or Lugui Qiu.

Additional information

Lugui Qiu and Yuqin Song are co-first authors of the article. Lugui Qiu and Jun Zhu are co-corresponding authors.

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Song, Y., Zhou, H., Zhang, H. et al. 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. Adv Ther 38, 1889–1903 (2021). https://doi.org/10.1007/s12325-020-01603-8

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Keywords

  • Biosimilar
  • CHOP
  • DLBCL
  • IBI301
  • Rituximab