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Found 1 Presentation For Request "287p"
287P - Efficacy, safety and pharmacokinetics of a proposed trastuzumab biosimilar HLX02 compared with trastuzumab in metastatic breast cancer: A global phase III study
- Qingyuan Zhang (Harbin, China)
Abstract
Background
HLX02 is a first CN-manufactured TZB biosimilar investigated in a global setting followed stringent biosimilar development guideline to increase patient accessibility worldwide. The confirmatory phase III study was aimed to evaluate equivalence in safety and efficacy of HLX02 and reference TZB in metastatic breast cancer (mBC) pts. Here we report the updates of efficacy and safety data up to 12 months and the PopPK model. The primary endpoints ORRwk24 was previously reported at ESMO 2019.
Methods
This is a multicountry, multicenter, randomized, double-blind, parallel-controlled equivalence study (HLX02-BC01). Eligible female pts were recruited and randomized at a 1:1 ratio to receive an IV dose 8mg/kg of HLX02 or EU-TZB combined with docetaxel on Day 1 followed by 6mg/kg in 3-week cycle up to 12 month. The primary endpoint was ORRwk24. The PopPK model was developed with the data collected from Ph1 and Ph3 study of HLX02 and reference TZBs (US- and EU-) in 754 subjects including healthy volunteers and previously untreated HER2+ mBC (serum sample=5882) pts using FOCEI method in non-linear mixed-effect modeling (NONMEM). Suitable covariates were selected using a forward addition and backward elimination method based on the significance levels of p<0.01 and p<0.001.
Results
The ORR was 71.3% (n=324) in HLX02 and 71.4% (n=325) in EU-TZB with the group difference of -0.1%, whose 95% CI (-7.0%, 6.9%) fell completely within the pre-defined equivalence margins of ±13.5%. No statistical difference was observed between 2 treatment groups in all secondary efficacy analyses (CBR, DCR, DoR, PFS and OS) up to 12 months. Safety outcomes and immunogenicity were similar. No significant difference was observed in steady state exposures (≤13% for AUCss and Cmax,ss) between HXL02 and TZBs in PopPK model. Covariates (e.g body weight) have influence on PK exposure show similarity between HLX02 and TZBs.
Conclusions
Based on the evidence of equivalent efficacy, safety and PK of HLX02 and reference TZBs in HER2+ mBC pts resulted from phase III trial and popPK model, HLX02 possesses the potential to provide alternative treatment option for pts globally.
Clinical trial identification
HLX02 phase I study: NCT02581748; HLX02 phase III study: NCT03084237.
Legal entity responsible for the study
Shanghai Henlius Biotech, Inc.
Funding
Shanghai Henlius Biotech, Inc.
Disclosure
Y. Li: Full/Part-time employment: Shanghai Henlius Biotech, Inc.. B. Shan: Full/Part-time employment: Shanghai Henlius Biotech, Inc.. S. Liu: Shareholder/Stockholder/Stock options, Officer/Board of Directors: Shanghai Henlius Biotech, Inc. W. Jiang: Shareholder/Stockholder/Stock options, Full/Part-time employment: Shanghai Henlius Biotech, Inc. X. Zhang: Full/Part-time employment: Shanghai Henlius Biotech, Inc. A. Luk: Full/Part-time employment: Shanghai Henlius Biotech, Inc. K. Chai: Full/Part-time employment: Shanghai Henlius Biotech, Inc. All other authors have declared no conflicts of interest.