A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers

• DOI: 10.1007/s00280-021-04297-z
• Publication Date: 2021-06-04T12:02:53Z
• Authors: Xiaoxue Zhu; Hongjie Qian; Jixuan Sun; Min Wu; Chen Yu; Yanhua Ding; Xiaodi Zhang; Katherine Chai; Xiaojiao Li
• Keywords: Bioequivalence; Clinical endpoint

Abstract Purpose To compare the pharmacokinetic profiles, safety and immunogenicity of proposed bevacizumab biosimilar HLX04 with reference in healthy Chinese males. Methods In this double-blind Phase 1 study, volunteers ( N = 208) were randomized 1:1:1:1 to a single 3 mg/kg intravenous infusion or sourced from United States (bevacizumab-US), European Union (bevacizumab-EU) China (bevacizumab-CN). Co-primary endpoints area under serum concentration–time profile (AUC) time zero extrapolated infinity (AUC 0–inf ) last quantifiable concentration ). Secondary endpoint was maximum drug (C max Study participants monitored for treatment-emergent adverse events (TEAEs) samples collected anti-drug antibody (ADA) testing throughout study. Results Pharmacokinetic parameters similar across groups. The respective geometric least-squares mean ratios (GLSMR) AUC , C were: 95.7%, 96.0% 101.8% versus bevacizumab-US; 94.3%, 94.6% 100.5% bevacizumab-EU; 90.0%, 90.4% 98.2% bevacizumab-CN. For all test-to-reference comparisons, two-sided 90% confidence intervals GLSMR fell pre-specified bioequivalence range (80–125%). There no notable differences frequency, nature and/or grade TEAEs. No deaths reported ADAs detected during Conclusion had profiles males, supporting confirmatory study investigating efficacy equivalence between patients metastatic colorectal cancer (NCT03511963). Clinical trial registration registered Clinicaltrials.gov, NCT03483649.