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. (2nd July 2020)

• Record Type: Journal Article
• Authors: Wang, Jiaxue; Niu, Suping; Dong, Wenliang; Wei, Li; Ou, Lun; Zhang, Tan; Zhang, Liangbi; Nie, Xiaoyan; Wang, Qian; Shen, Tiantian; Wang, Qi; Xia, Lin; Liu, Gang; Jin, Jiting; Zheng, Qingshan; Song, Haifeng; Fang, Yi
• Is Part Of: Expert opinion on investigational drugs. Volume 29:Number 7(2020)
• Page Start: 755
• Page End: 762
• Publication Date: 2020-07-02
• Subjects: Trastuzumab -- biosimilar -- pharmacokinetic -- female Subjects -- pre-treatment -- phase I; Drugs -- Design -- Periodicals; Drugs, Investigational -- Bibliography; Drugs, Investigational -- Periodicals; 615.1
• DOI: 10.1080/13543784.2020.1770226
• Languages: English
• ISSNs: 1354-3784

Abstract

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 (AUC0-t ) and peak concentration in serum (Cmax ). 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..