First China-Manufactured Proposed MabThera® Biosimilar Met Primary Efficacy and Safety Endpoints in CD20-Positive Diffuse Large B-Cell Lymphoma

Date 24 November 2018
Event ESMO Asia 2018 Congress
Session Poster display - Cocktail
Topics Anticancer Agents
Clinical Research
Presenter Yuankai Shi
Citation Annals of Oncology (2018) 29 (suppl_9): ix87-ix93. 10.1093/annonc/mdy437
Authors Y. Shi1, Q. Zhang2, X. Han3, Y. Song4, Y. Qin1, X. Hong5, X. Ke6, J. Feng7, D. Wang8, W. Li9, H. Su10, Y. Zhang11, H. Zhang12, J. Yang13, L. Liu14, X. Zhang15, E. Liu15, W. Jiang16, S. Liu16, A. LUK17
  • 1Internal Medicine Oncology, Cancer Hospital Chinese Academy of Medical Sciences, 10021 - Beijing/CN
  • 2Internal Medicine, Harbin Medical University Cancer Hospital, Harbin/CN
  • 3Clinical Trial Office, Cancer Hospital Chinese Academy of Medical Sciences, 10021 - Beijing/CN
  • 4Haemotology,  Henan Cancer Hospital, Zhengzhou/CN
  • 5Internal Medicine Oncology, Fudan University Shanghai Cancer Center, Shanghai/CN
  • 6Haemotology, Peking University Third Hospital, Beijing/CN
  • 7Internal Medicine Oncology, Jiangsu Cancer Hospital, Nanjing/CN
  • 8Oncology, The Third Affiliated Hospital and Research Institute of Surgery of Army Medical University, Chongqing/CN
  • 9Cancer Center, The First Bethune Hospital of Jilin University, Changchun/CN
  • 10Internal Medicine Oncology, The 307th Hospital of Military Chinese People's Liberation Army, Beijing/CN
  • 11Oncology, The 2nd Hospital of DaLian Medical University, DaLian/CN
  • 12Haematology, TianJin Medical Univerisity Cancer Institute and Hospital, TianJin/CN
  • 13Haematology, Changhai Hospital of Shanghai, Shanghai/CN
  • 14Internal Medicien, Tangdu Hospital of Fourth Medical University , Xian/CN
  • 15Global Clinical And Medical Affairs, Shanghai Henlius Biopharm, 200233 - Shanghai/CN
  • 16Executive Office, Shanghai Henlius Biopharm, 200233 - Shanghai/CN
  • 17Global Clinical And Medical Affairs, Shanghai Henlius Biotech,Inc., 200233 - Shanghai/CN



While rituximab (rituximab) has revolutionized the treatment of B-cell lymphoma (BCL), its high manufacturing cost and lack of lower-priced competition have driven up prices resulting in limited access to treatment for millions of patients. HLX01 was developed as a rituximab biosimilar with the potential to increase market competition and treatment accessibility.


Upon successful demonstration of equivalence in safety, PK/PD in previously-treated patients with CD20(+) BCL, we subsequently conducted a multi-center, double-blind, randomized, parallel-control Phase 3 study comparing the primary efficacy in best objective response rate (ORR) and safety profiles for six 3-week cycle treatments of 375mg/m2 either HLX01 with cyclophosphamide, doxorubicin, vincristine and prednisone (H-CHOP) or rituximab CHOP (R-CHOP) in patients with treatment-naïve CD20+ diffuse large B cell lymphoma (DLBCL).


A total of 81 CD20(+) BCL patients who have reached complete response (CR) or CR uncertain (CRu) after treatment was randomized to receive a single infusion of 375mg/m2 either HLX01 (n = 40) or rituximab-CN (n = 41). The geometric means ratio for AUC0-91D and Cmax [90% CIs] were 0.90 [0.81-1.00] and 1.03 [0.95 -1.11], respectively. The baseline CD19+/CD20(+) B-cell counts were reduced and remained over 95% depletion for up to 91 days; safety profiles were similar in both treatment groups. Subsequently, a total of 407 CD20+ DLBCL patients was randomized; 402 patients (H-CHOP:199; R-CHOP:203) in the full analysis set (FAS) and 382 patients (H-CHOP:188; R-CHOP:194) in per protocol study (PPS) were evaluated. As compared H-CHOP with R-CHOP, the ORR analysis of the FAS was 92.5% and 92.0% with δ (equivalence margin difference) of 0.3% [95% CI: -4.87% to 5.56%; p = 0.839] and the PPS was 94.1% and 92.8% with δ of 1.4% [95% CI: -3.59% to 6.32%; p = 0.608], respectively. Number of AEs, SAEs and detection of anti-drug antibodies was comparable between H-CHOP and R-CHOP groups.


We report successful demonstration of equivalence in, PK/PD, efficacy and safety between HLX01 and rituximab sourced from China. Furthermore, HLX01 does not demonstrate new safety signals in comparison with rituximab.

Editorial acknowledgement

Clinical trial identification

NCT02787239; CDE-registration Number: CTR20150583.

Legal entity responsible for the study

Shanghai Henlius Biotech, Inc.


Shanghai Henlius Biotech, Inc.


X. Zhang, A. Luk: Employment: Shanghai Henlius Biotech, Inc.E. Liu: Employment: Henlix Biotech, Inc. W. Jiang, S. Liu: Employment: Shanghai Henlius Biotech, Inc; Stock ownership: Shanghai Henlius, Inc. All other authors have declared no conflicts of interest.