A randomized, double-blind, single-dose, single-center, parallel phase I clinical study comparing the pharmacokinetics, immunogenicity, safety, and tolerance of pertuzumab injection and Perjeta® in healthy Chinese male subjects

Abstract

Background

Perjeta® is a recombinant, humanized monoclonal antibody that has been marketed and approved for the targeted therapy of human epidermal growth factor receptor (HER2) positive breast cancer in the United States. This study compared the bioequivalence, immunogenicity, and safety of pertuzumab injection (a biosimilar of Perjeta® produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Perjeta® (produced by Roche Pharma AG) in healthy Chinese males.

Research design and methods

Healthy Chinese male subjects (N = 87) were randomly given intravenous injection of 5 mg/kg pertuzumab or Perjeta® at a 1:1 ratio. Plasma drug concentrations were detected by enzyme-linked immunosorbent assay, and primary pharmacokinetic parameters were statistically analyzed. We detected the levels of anti-drug antibody (ADA) and neutralizing antibody (nAb) to evaluate drug immunogenicity and safety of the drugs throughout the study.

Results

The geometric mean ratios of AUC_0-t, C_max, and AUC_0-∞ for pertuzumab and Perjeta® were 100.42%, 96.71%, and 101.47%, respectively. The 90% CIs were all within 80%–125%, meeting the bioequivalence standards. The levels of ADA and nAb were similar. In addition, both had good safety in the study.

Conclusion

The study shows that pertuzumab injection and Perjeta® had similar bioequivalence, immunogenicity, and safety.

KEYWORDS:

• Pertuzumab injection
• Perjeta®
• HER2
• bioequivalence
• immunogenicity
• safety

Supplemental data

Supplemental data for this article can be accessed here.

Clinical trial registration

The trial is registered at the Chinese Clinical Trial website

(http://www.chinadrugtrials.org.cn/index.html # ZDTQ-2018-PTZDK)

Declaration of interests

All data related to this study were interpreted by the trial staff with complete independence from the sponsor. Zhongnan Xu, Jinling Xue are employees of Chia Tai Tianqing Pharmaceutical Group Co., Ltd; Guangwen Liu, Wei Yang, Yanli Wang, Zhengzhi Liu, Yingzi Cui, Xinyao Qu, Tianying Chang, Shuang Yu, Yang Cheng, Yannan Zhou, Jiahui Chen, Qing Ren and Wanhua Wang, Zeyu Wang and Haimiao Yang are employees of Affiliated Hospital of Changchun University of Chinese Medicine; and Qiaohuan Deng is a graduate student of Changchun University of Chinese Medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with financial interest in or financial with the subject matter or materials discussed in the manuscript apart from those disclosed.

Data Availability Statement

We confirm that the figures and tables in the manuscript are original and have not been published before. The data that support the findings of this study are available from the corresponding author upon reasonable request but remain subject to all applicable legal requirements to protect the confidentiality of the study participants’ personal information

Acknowledgments

Chia Tai Tianqing Pharmaceutical Group Co., Ltd. provided the drugs (pertuzumab injection and reference pertuzumab). Thanks to all enrolled participants, investigators, and people who contributed to this study. Thanks to Yicheng Zhao from Changchun University of Chinese Medicine and the graduate student of Jilin University Xinran Ren for assisted in drafting the manuscript.

Author Contributions

Guangwen Liu, Zhongnan Xu, Zeyu Wang, and Haimiao Yang were involved in the conception and design of the trial; Wei Yang, Jinling Xue, Yanli Wang, Zhengzhi Liu, Yingzi Cui, Xinyao Qu, Tianying Chang, Shuang Yu, Yang Cheng, Yannan Zhou, Jiahui Chen, Qing Ren, and Wanhua Wang performed the research, Qiaohuan Deng edited the paper and drew the figures; Zeyu Wang and Haimiao Yang finally approved of the version. All authors agreed to be accountable for all aspects of the work.

Additional information

Funding

This work was supported by Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Jiangsu, China, funding number: phase I 2019-004. The founder helps pay for this study and has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.