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01-03-2021 | Pharmacokinetics | Original Article

A Phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX02 to reference CN- and EU-sourced trastuzumab in healthy subjects

Authors: X. Zhu, Y. Ding, Y. Yu, M. Wang, W. Zhou, J. Wang, X. Zhu, H. Zhang, M. Wang, K. Chai, X. Zhang, A. Luk, W. Jiang, S. Liu, Q. Zhang

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2021

Abstract

Purpose

This study evaluated the bioequivalence of China-manufactured biosimilar, HLX02, to reference China (CN)- and European Union (EU)-sourced trastuzumab.

Methods

This was a two-part Phase 1 study conducted in healthy Chinese males. Part 1 evaluated the safety of different doses of HLX02 (2, 4, 6 or 8 mg/kg; intravenous infusion over 90 min, n = 3 per group). Part 2, a randomized, double-blind study, investigated the pharmacokinetics (PK), safety and immunogenicity of study drugs (HLX02 [n = 37], CN-trastuzumab [n = 35] or EU-trastuzumab [n = 37] at the dose suggested by Part 1 results). The primary PK endpoint was the area under the serum concentration–time curve from time 0 to infinity (AUC_inf). Equivalence was concluded if the 90% confidence interval (CI) for the geometric least squares mean ratio (GLSMR) fell in the equivalence criteria of 0.80–1.25.

Results

In Part 1, all doses of HLX02 were well tolerated and 6 mg/kg was suggested for Part 2. The GLSMRs and 90% CIs for AUC_inf were: 0.950 (0.891–1.013), 0.914 (0.858–0.973) and 0.962 (0.902–1.025) for HLX02 versus CN-trastuzumab, HLX02 versus EU-trastuzumab and CN-trastuzumab versus EU-trastuzumab, respectively. Secondary endpoints comparisons also fell in the equivalence criteria. Treatment-emergent adverse events were reported in 75.7, 86.5 and 70.3% of the subjects in HLX02, CN-trastuzumab, and EU-trastuzumab groups, respectively. No serious adverse events or deaths occurred. No treatment-related anti-drug antibodies were detected.

Conclusion

This study demonstrated comparable safety profiles and PK bioequivalence among HLX02, CN-trastuzumab and EU-trastuzumab in healthy Chinese male subjects.

Clinical trial registration

ClinicalTrials.gov, NCT02581748, registered at October 19, 2015.

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Title: A Phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX02 to reference CN- and EU-sourced trastuzumab in healthy subjects
Authors: X. Zhu
Y. Ding
Y. Yu
M. Wang
W. Zhou
J. Wang
X. Zhu
H. Zhang
M. Wang
K. Chai
X. Zhang
A. Luk
W. Jiang
S. Liu
Q. Zhang
Publication date: 01-03-2021
Publisher: Springer Berlin Heidelberg
Keywords: Pharmacokinetics
Breast Cancer
Breast Cancer
Trastuzumab
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2021
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04196-9

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Abstract

Purpose

Methods

Results

Conclusion

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