A randomized phase I clinical trial comparing the pharmacokinetic, safety, and immunogenicity of potential biosimilar recombinant human HER2 monoclonal antibody for injection and trastuzumab in healthy Chinese adults

ABSTRACT

Objectives

Recombinant human HER2 monoclonal antibody for injection (AK-HER2) is a potential biosimilar of trastuzumab (Herceptin®). This phase Ⅰ study aimed to demonstrate the pharmacokinetic (PK) equivalence between AK-HER2 and trastuzumab in healthy volunteers. Besides, safety and immunogenicity were investigated.

Research design and methods

This was a randomized, double-blind phase Ⅰ trial in 96 healthy adults who received a single intravenous infusion of AK-HER2 or trastuzumab at 6 mg/kg. The primary PK endpoints were area under the serum concentration curve (AUC) from time 0 to the last time point (AUC_0-t) and peak concentration in serum (C_max). The PK bioequivalence was confirmed using the standard equivalence margins of 80%-125%.

Results

The PK profiles of AK-HER2 and trastuzumab displayed high similarity. The geometric mean ratios (90% confidence intervals) of primary PK endpoints were within 80%-125%. The C _max and AUC _0-t of female subjects in the AK-HER2 group were greater than those of male subjects (P <0.05). No infusion-related reactions (IRRs) or anti-drug antibody-positivity was observed after dosing.

Conclusions

AK-HER2 was demonstrated to have highly similar PK to trastuzumab in healthy Chinese adults. Both drugs showed comparable safety and immunogenicity using dexamethasone as premedication to prevent IRRs..

KEYWORDS:

• Trastuzumab
• biosimilar
• pharmacokinetic
• female Subjects
• pre-treatment
• phase I

Author contributions

Jiaxue Wang and Suping Niu contributed equally to this work. Yi Fang, Haifeng Song, Qingshan Zheng, Xiaoyan Nie, Jiting Jin, Liangbi Zhang, and Li Wei designed and monitored the whole study. Jiaxue Wang and Suping Niu contributed to the data analysis and paper writing equally. Gang Liu and Qian Wang were responsible for pre-treatment, drug administration, and blood sample collection in this study. Wenliang Dong, Tan Zhang, Qi Wang, Tiantian Shen and Lin Xia contributed to blood sample collection and data analysis. Haifeng Song and Lun Ou were in charge of determination of drug concentrations. All authors provided critical review and approved this manuscript. Yi Fang is the guarantor for the overall content.

Acknowledgments

Anhui Anke Biotechnology (Group) Co., Ltd. (Anhui, China.) provided the drugs (AK-HER2 and reference trastuzumab). The authors would like to extend thanks to all enrolled participants, investigators, and people who contributed to this study.

Declaration of interest

Li Wei, Liangbi Zhang and Jiting Jin are employees of Anhui Anke Biotechnology (Group) Co., Ltd. (Anhui, China.). 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

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Supplementary material

Supplemental data for this artcile can be accessed here.

Additional information

Funding

This study was fully funded by Anhui Anke Biotechnology (Group) Co., Ltd. (Anhui, China.), funding number: phase I 2016-01.