Abstract <p>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&#xa0;mg (14&#xa0;mL) intravenous infusion of SYSA1901 or pertuzumab (Perjeta®), respectively. Primary endpoint: serum concentration–time curve area from 0 to infinity (<i>AUC</i>_0–∞). Secondary endpoints: AUC from 0 to last quantifiable concentration (<i>AUC</i>_0–t), maximum serum concentration (<i>C</i>_max), safety, and immunogenicity. For the key PK parameters of SYSA1901 relative to Perjeta®, the geometric mean ratios (GMRs) were as follows: <i>AUC</i>_0–∞ at 90.23% (95% CI: 84.41%–96.45%), <i>AUC</i>_0–t at 90.25% (95% CI: 84.48%–96.42%), and <i>C</i>_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.</p> Trial registration <p>This trial was registered on the Chinese Clinical Trial Registry (URL: <a href="http://www.chinadrugtrials.org.cn/index.html">http://www.chinadrugtrials.org.cn/index.html</a>) under Test Protocol No. SYSA1901-001 and Registration No. CTR20212874. Registration date: 3 September 2021.</p>