Comparing the pharmacokinetics, safety, and immunogenicity of HLX02 to US- and EU-approved trastuzumab in healthy Chinese male subjects: A Phase I, randomized, double-blind, parallel-group study

ABSTRACT

Background

HLX02, the first China-manufactured trastuzumab biosimilar, is approved in Europe (EU) and China. This study evaluated bioequivalence between HLX02 and US-approved trastuzumab (US-trastuzumab).

Method

In this double-blind, parallel-group, Phase I study, healthy Chinese men were randomized (1:1:1) to receive a single 6 mg/kg dose of HLX02, reference US-trastuzumab, or reference EU-approved trastuzumab (EU-trastuzumab). Equivalence in PK profiles was demonstrated if the 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for the difference between the least square means of the area under the curve (AUC) from time 0 to infinity (AUC_∞) were 0.8–1.25.

Results

Pharmacokinetic profiles of the three trastuzumab products were similar in 111 Chinese men. Equivalence was confirmed between HLX02 and US-trastuzumab (GMR for AUC_∞ 1.009, 90% CI 0.950–1.072); HLX02 and EU-trastuzumab (GMR for AUC_∞ 1.068, 90% CI 1.005–1.135); and EU- and US-trastuzumab (GMR for AUC_∞ 0.945, 90% CI 0.889–1004). Exploratory analysis of all other PK parameters also demonstrated equivalence between any two of the three trastuzumab products. HLX02 had similar safety and immunogenicity profiles to US- and EU-trastuzumab.

Conclusion

HLX02 is bioequivalent to US-trastuzumab and EU-trastuzumab, with similar safety and immunogenicity profiles. US- and EU-trastuzumab were also bioequivalent to each other.

KEYWORDS:

• Trastuzumab
• pharmacokinetics
• bioequivalence
• biosimilar
• immunogenicity

Acknowledgments

We thank all of the participants in the trial, their families, clinical staff at the study center, and the clinical study team (Clinical Operation: Qiong Lin; Clinical Development: Futang Yang; Statistics: Wenting Qiu, Jiancheng Cheng; Pharmacokinetics: Qian Wang), and Wenjie Zhang of Shanghai Henlius Biotech, Inc. for providing support for the study. Medical writing support was provided by Jake Burrell of Rude Health Consulting Ltd, and Zhi Hao Kwok, Shiqi Zhong, and Chen Hu of Shanghai Henlius Biotech, Inc.

Declaration of interest

G Yang, H Yu, J Li, and L Zhou are employees of Shanghai Henlius Biotech, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are principal investigators of SB3 and HD201 development, trastuzumab biosimilars comparable to HLX02. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Ethics statement

The study protocol was approved by the ethics committee of the Second Affiliated Hospital of Soochow University, Suzhou, China. This study was conducted with respect for the individual participants (i.e. subjects), according to the protocol, the World Medical Association Declaration of Helsinki, the ICH-GCP guideline, and applicable local regulatory requirements of each participating region. Written informed consent was obtained from all participants.

Author contributions

Q Zhang contributed to the study design and conception. All authors contributed to the data analysis, interpretation, and manuscript writing and editing. All authors reviewed and approved the final manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14712598.2023.2183117

Additional information

Funding

This paper was funded by Shanghai Henlius Biotech, Inc.