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Poster display - Cocktail

1014 - Global Clinical Trials Validating Bioequivalence with China-Manufactured Trastuzumab Biosimilar, HLX02, and Herceptin®


24 Nov 2018


Poster display - Cocktail


Cytotoxic Therapy;  Clinical Research

Tumour Site

Breast Cancer


Quanying Zhang


Annals of Oncology (2018) 29 (suppl_9): ix13-ix20. 10.1093/annonc/mdy428


Q. Zhang1, B. Xu2, Q. Zhang3, T. Sun4, W. Li5, Y. Teng6, X. Hu7, I. Bondarenko8, H. Adamchuk9, L. Zhang10, D. Trukhin11, S. Wang12, H. Zheng13, Z. Tong14, X. Zhang15, E. Liu15, W. Jiang16, S. Liu16, A. LUK15

Author affiliations

  • 1 Department Of Clinical Pharmacology, The Second Affiliated Hospital of Soochow University, 215004 - Suzhou/CN
  • 2 Internal Medicine Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing/CN
  • 3 Medical Oncology, Harbin Medical University Cancer Hospital, Harbin/CN
  • 4 Internal Medicine Oncology, Liaoning Cancer Hospital, Liaoning/CN
  • 5 Internal Medicine Oncology, The First Bethune Hospital of Jilin University, Jilin/CN
  • 6 Internal Medicine Oncology, The First Hospital of China Medical University, Shenyang/CN
  • 7 Internal Medicine Oncology, Shanghai Cancer Hospital, Fudan University, Shanghai/CN
  • 8 Chemotherapy Department, Communal Institution Dnipropetrovsk City Multifield Clinical Hospital, Dnipro/UA
  • 9 Chemotherapy Department, Communal Institution Kryvyl Rih Oncological Dispensary of Dnipropetrovsk Regional Council, Kryvyl Rih/UA
  • 10 Internal Medicine Oncology, Yantai Yuhuangding Hospital, Yant/CN
  • 11 Daystay Care Of Dispensary And Policlinic Department, Communal Institution Odesa Regional Oncological Dispensary, Odesa/UA
  • 12 Internal Medicine Oncology, Sun Yat-sen University, Cancer Center, Guangzhou/CN
  • 13 Internal Medicine Oncology, West China Hospital, Sichuan University, Sichuan/CN
  • 14 Internal Medicine Oncology, Tianjin Cancer Hospital, Tianjin/CN
  • 15 Global Clinical And Medical Affairs, Shanghai Henlius Biopharm, 200233 - Shanghai/CN
  • 16 Executive Office, Shanghai Henlius Biopharm, 200233 - Shanghai/CN

Abstract 1014


HLX02 is being developed to address the current global need for high-quality yet affordable trastuzumab biosimilar (trastuzumab) for patients with breast cancer.


Following the step-wise clinical approach for the development of biosimilar, we first enrolled 12 healthy males to evaluate safety and tolerability after a single infusion of HLX02 at 2, 4, 6 and 8 mg/kg. Upon successful demonstration of safety and PK (AUC0-∞, Cmax, AUC0-tau) equivalence between HLX02 and reference trastuzumab in 109 healthy males received a single infusion of 6 mg/kg either HLX02, trastuzumab sourced from EU or US, we subsequently conducted a multi-national, randomized, double-blind, parallel-controlled, phase 3 study (HLX02-BC01) investigating the efficacy and safety profiles of HLX02 and trastuzumab-EU with docetaxel in adult females with HER2+ breast cancer from 83 centers in 4 countries. The primary efficacy endpoint was best overall response rate up to week 24 (ORR24), and safety endpoints included immunogenicity and incidence of adverse events.


After different concentrations of HLX02 demonstrated acute and dose-dependent effect on serum concentration of 12 healthy males in a phase 1a clinical trial, a total of 109 healthy males was randomized to receive 6mg/kg of HLX02 (n = 37),trastuzumab-EU(n = 37) or trastuzumab-US(n = 35). The geometric mean ratio of the AUC0-∞ [90% confidence intervals] for HLX02 / trastuzumab-EU, HLX02 / trastuzumab-US and trastuzumab-US / trastuzumab-EU were 0.914 [0.858-0.973], 0.950 [0.891-1.013] and 0.962 [0.902-1.025], respectively, all within the bioequivalence margin of 0.80-1.25 (Table). No deaths, SAE or ADA-positive results were observed in any of the treatment groups. Based on these results, 653 previously-untreated females with HER2-overexpressing metastatic breast cancer in China, Poland, Ukraine and Philippines were randomized in an ongoing phase 3 pivotal study.Table: 44P

Pairwise comparison of AUC0-∞ between HLX02, trastuzumab-EU and trastuzumab-US

Comparison with Different ProductsnAUC0-∞ Geo- LSMean (μg·h/mL)AUC0-∞ Ratio A/BAUC0-∞ 90% CI of Ratio
HLX02 vs trastuzumab-EU37 3719805.4 21679.00.914(0.858-0.973)
HLX02 vs trastuzumab-US37 3519805.4 20847.30.950(0.891-1.013)
trastuzumab-US vs trastuzumab-EU35 3720847.3 21679.00.962(0.902-1.025)


The three-way PK and safety equivalence of HLX02 and reference trastuzumab were demonstrated leading to the pivotal phase 3 study which has completed the enrolment in June 2018. To the best of our knowledge, the ongoing phase 3 study was the first China-manufactured trastuzumab biosimilar being investigated in a global setting.

Editorial acknowledgement

Clinical trial identification

NCT03084237 and EudraCT-ID: 2016-000206-10.

Legal entity responsible for the study

Shanghai Henlius Biotech, Inc.


Shanghai 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.

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