The Updated Multi-Centre Phase 3 Clinical Study Data of Trastuzumab 汉曲优® Released in ESMO

The 2020 annual meeting of the European Society for Medical Oncology (ESMO) will be held on 19th September to 18th October. At this conference, Henlius released the updated multi-centre Phase 3 clinical study of Trastuzumab 汉曲优® (HLX02, EU brand name: Zercepac®). What’s more, the clinical benefit rate (CBR), disease control rate (DCR), duration of response (DoR) and progression-free survival (PFS) of the study will also be released at the 12th European Breast Cancer Conference (EBCC), and the abstract will be released on 18th September, the E-poster will be released on 2nd October.

Details of HLX02 study at ESMO are as follows:

Title: Efficacy, Safety and Pharmacokinetics of a Proposed Trastuzumab Biosimilar HLX02 Compared with Trastuzumab in Metastatic Breast Cancer: A Global Phase 3 Study

Poster number: 287P

Form: E-poster

Presenter: Bing-He Xu, M.D., Ph.D.

Time: 09:00 (CEST) 17th Sept. 2020 – 20:00 (CEST) 21st Sept. 2020

Place: ESMO Congress platform (Online)

汉曲优 (trastuzumab biosimilar, EU brand name: Zercepac) is developed by Henlius independently. The development process strictly followed the National Medical Products Administration (NMPA) and European Medicines Agency (EMA) biosimilar guidelines, and 汉曲优 has been approved by the NMPA and the European Commission (EC) recently, making it the first China-developed monoclonal antibody (mAb) biosimilar to be approved both in China and in the EU. The HLX02 Phase 3 study (HLX02-BC01, NCT03084237 and EudraCT: 2016-000206-10) is a multi-centre, randomised, double-blind, parallel-controlled trial in patients with recurrent or metastatic HER2-positive breast cancer who had not received prior systemic treatment to demonstrate equivalence in the efficacy, safety and pharmacokinetics between HLX02 and European Union (EU)-sourced trastuzumab (TZB). Professor Binghe Xu, Cancer Hospital Chinese Academy of Medical Sciences is the principle investigator of this study. Henlius has presented a part of sub-group analysis results of this HLX02 Phase 3 clinical trial at CSCO in 2019 and the Week 24 efficacy and safety results from different analysis sets at ESMO and ESMO Asia in 2019. Here, we reported the updated 1-year efficacy and safety results of the Phase 3 study and the PopPK model.

Study design

In the multi-centre, randomised, double-blind, parallel-controlled HLX02-BC01 Phase 3 study (NCT03084237, EudraCT: 2016-000206-10), patients with HER2-positive recurrent or metastatic breast cancer who had not received prior systemic treatment were randomised (1:1) to receive either HLX02 or European Union (EU) – sourced trastuzumab (TZB) in combination with docetaxel in a 3-week cycle for up to 1 year. The primary endpoint was overall response rate after 8 treatment cycles at Week 24 (ORRwk24). The PopPK model was developed with the data from the HLX02-BC01 and HLX02-HV01 (NCT02581748) studies (HLX02, N=356; TZBs, N=398; Serum sample, N=5882) using non-linear mixed-effect modelling (NONMEM) with the first-order estimation with interaction (FOCEI) method. Important covariates (e.g. demographics, pathophysiologic and disease conditions) were included in model characterisation for the evaluation of pharmacokinetic-pharmacodynamic (PK-PD) correlation. A total of 1,000 simulations were tested using the observed covariates.


  • Efficacy-Primary endpoint

    649 patients were enrolled (HLX02, N=324; EU-TZB, N=325). Per ITT set, ORRwk24 was 71.3% in HLX02 group and 71.4% in EU-TZB group, and the group difference was -0.1% (95% CI: -7.0%, 6.9%). Per PP set, ORRwk24 was 74.2% in HLX02 group and 73.2% in EU-TZB group, and the group difference was 1.0% (95% CI: -6.0%, 7.9%).The group differences in ITT and PP sets both fell entirely in the pre-defined equivalence margins (±13.5%). All subgroup analyses (Asian vs. non-Asian, and Chinese vs. non-Chinese) showed no statistically significant differences (p >0.05) in ORR between the treatment groups in all populations, demonstrating the equivalence in efficacy.

  • Efficacy-Secondary endpoints

    There was no statistically significant difference between the two treatment groups (p >0.05) in secondary endpoints, including clinical benefit rate (CBR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS).

  • Safety

    The safety profiles (including the incidence rate of drug related cardiac disorders) were similar between HLX02 and reference TZB.

  • PopPK

    The PopPK model was described by a two-compartment model with first-order elimination. No statistically significant difference in steady state exposures (≤13% for AUCss and Cmax,ss) was observed between HLX02 and TZBs in the PopPK model. The influence of covariates (e.g. body weight) on PK exposure was similar between the HLX02 and TZBs treatment groups.


The results of the Phase 3 study and the PopPK model demonstrated the equivalent efficacy and similar safety and PK between HLX02 and reference TZB in patients with HER2-positive metastatic breast cancer. HLX02, as the first approved China (CN) – manufactured TZB biosimilar, will be able to provide alternative treatment option for patients globally.

Parag Narang

Parag Narang is a Digital Marketing Associate at PharmaShots, a division of Octavus Consulting. He manages the digital marketing as well as the designing ideas for PharmaShots. He has a degree in Bachelor of Business Administration along with Post Graduate Program in Management (Marketing). Parag manages all the social media handles very well since he has a good experience in Marketing & Sales.

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