Phase I randomized double-blind parallel-group study: pharmacokinetics, safety, and immunogenicity of pertuzumab...

Pertuzumab, administered as an injection, is an antagonist of human epidermal growth factor receptor 2 (HER2). This study sought to compare the pharmacokinetic (PK) profiles, safety, and immunogenicity between pertuzumab biosimilar SYSA1901 injection and the reference product (Perjeta®) in healthy males. In this single-center, randomized, double-blind, parallel-group, single-dose trial, 88 male subjects were enrolled and randomized into two groups, each receiving a single 420 mg (14 mL) intravenous infusion of SYSA1901 or pertuzumab (Perjeta®), respectively. Primary endpoint: serum concentration-time curve area from 0 to infinity (AUC_0-∞). Secondary endpoints: AUC from 0 to last quantifiable concentration (AUC_0-t), maximum serum concentration (C_max), safety, and immunogenicity. For the key PK parameters of SYSA1901 relative to Perjeta®, the geometric mean ratios (GMRs) were as follows: AUC_0-∞ at 90.23% (95% CI: 84.41%-96.45%), AUC_0-t at 90.25% (95% CI: 84.48%-96.42%), and C_max at 94.69% (95% CI: 90.46%-99.12%). All GMRs fell within the pre-specified bioequivalence range of 80.00%-125.00%. SYSA1901 and Perjeta® demonstrated comparable PK profiles, with no clinically significant differences in safety or immunogenicity. In this study, SYSA1901 injection and Perjeta® showed similar PK profiles, safety, and immunogenicity. These findings support further clinical investigations of the investigational drug in breast cancer. TRIAL REGISTRATION: This trial was registered on the Chinese Clinical Trial Registry (URL: http://www.chinadrugtrials.org.cn/index.html ) under Test Protocol No. SYSA1901-001 and Registration No. CTR20212874. Registration date: 3 September 2021.