HLX11, a Proposed Pertuzumab Biosimilar: Pharmacokinetics, Immunogenicity, and Safety Profiles Compared to Three Reference Biologic Products (US-, EU-, and CN-Approved Pertuzumab) Administered to Healthy Male Subjects

Jingjing Yang, Lili Lin, Qihe Long, Qian Zhang, Guilan Sun, Liang Zhou, Qingyu Wang, Jun Zhu, Fanfan Li, Wei Hu, Jingjing Yang, Lili Lin, Qihe Long, Qian Zhang, Guilan Sun, Liang Zhou, Qingyu Wang, Jun Zhu, Fanfan Li, Wei Hu

Abstract

Background: Pertuzumab is a humanized monoclonal antibody for the treatment of breast cancer. HLX11 is a biosimilar of pertuzumab developed by Shanghai Henlius Biotech, Inc. We conducted a bioequivalence study for HLX11 and pertuzumab (United States [US]-, European Union [EU]-, and China [CN]-approved products).

Objectives: This study compared the biosimilarity in pharmacokinetics (PK), safety, and immunogenicity between HLX11 and reference pertuzumab (approved in the US, the EU, and CN) in healthy Chinese male participants after a single infusion and further characterized the PK profile of HLX11.

Methods: Eligible individuals were randomized 1:1:1:1 to receive a single dose of 420 mg HLX11, US-, EU-, or CN-pertuzumab via intravenous infusion over 60 min. The primary endpoints were maximum serum drug concentration (Cmax), area under the serum concentration-time curve (AUC) from time 0 to time of the last quantifiable concentration (AUC0-t), and AUC from time 0 to infinity (AUC0-∞). PK bioequivalence was established if the 90% confidence intervals (CIs) of the geometric mean ratios of the primary endpoints were between 80.0 and 125.0%. Secondary endpoints included other PK parameters, safety, and immunogenicity.

Results: A total of 160 participants were enrolled and randomly assigned to each group (n = 40 per group). The 90% CIs of the geometric mean ratios of the primary endpoints were all within the prespecified equivalence margins (HLX11 vs. pertuzumab [US-, EU-, CN-approved products]: Cmax 97.03-115.06%, 91.39-109.80%, 94.53-110.65%; AUC0-t 87.65-99.68%, 87.07-100.79%, 86.29-101.09%; AUC0-∞ 87.66-99.90%, 87.54-101.05%, 89.23-103.20%). The incidence of adverse drug reactions was comparable across the four groups. The presence of anti-drug antibodies or neutralizing antibodies had no obvious effect on PK.

Conclusion: The PK, safety, and immunogenicity of HLX11 were highly similar to those of reference pertuzumab (US-, EU-, CN-approved products). The established bioequivalence supports further clinical trials of HLX11 in cancer treatment.

Trial registration: This study was registered with ClinicalTrials.gov (NCT04411550) and Chinadrugtrials.org.cn (CTR20200618).

Conflict of interest statement

Guilan Sun, Liang Zhou, Qingyu Wang, and Jun Zhu are employees of Shanghai Henlius Biotech, Inc. All other authors declare that there are no conflicts of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study design and patient flow diagram. CN China, EU European Union, ICF Informed Consent Form, PK pharmacokinetic, PKS PK analysis set, SS safety set, US United States
Fig. 2
Fig. 2
The mean serum concentration (mean ± SD)–time profiles by treatment (linear and semilogarithmic scale) (PKS). A The mean serum concentration–time profiles (linear scale), mean (± SD). B The mean serum concentration–time profiles (semilogarithmic scale). CN China, EU European Union, PK pharmacokinetic, PKS PK analysis set, SD standard deviation, US United States
Fig. 3
Fig. 3
The effect of immunogenicity on serum concentration (mean ± SD) (linear and semilogarithmic scales). A Serum concentration–time profiles stratified by ADA results (linear scale) (PKS), mean (± SD). B Serum concentration–time profiles stratified by ADA results (semilogarithmic scale) (PKS), mean (± SD). C Serum concentration–time profiles stratified by NAb results (linear scale) (PKS), mean (± SD). D Serum concentration–time profiles stratified by NAb results (semilogarithmic scale) (PKS), mean (± SD). ADA anti-drug antibody, CN China, EU European Union, NAb neutralizing antibody, PK pharmacokinetic, PKS PK analysis set, SD standard deviation, US United States

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Source: PubMed

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