A Global Phase I Clinical Study Comparing the Safety and Pharmacokinetics of Proposed Biosimilar BAT1706 and Bevacizumab (Avastin®) in Healthy Male Subjects

• Published in: BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy Vol. 33; no. 3; pp. 335 - 342
• Main Authors: Wu, Xiaoyun, Wynne, Chris, Xu, Chenchao, Gan, Yiting, Wang, Chaohe, Thomas, Bert E., Yu, Jin-Chen, Li, Shengfeng, Zhang, Li
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2019; Springer Nature B.V
• Subjects: Adverse events; Antibodies; Bevacizumab; Biological products; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Clinical trials; Drug dosages; Electrocardiography; FDA approval; Immunoassay; Immunogenicity; Immunotherapy; Intravenous administration; Medical laboratories; Molecular Medicine; Monoclonal antibodies; Original Research Article; Patients; Pharmacokinetics; Pharmacotherapy; Regulatory agencies; Safety; Sample size; Targeted cancer therapy; Vascular endothelial growth factor; Vital signs; United States > US; China
• ISSN: 1173-8804; 1179-190X; 1179-190X
• DOI: 10.1007/s40259-019-00352-7

Objective BAT1706 is a proposed biosimilar of bevacizumab (BEV). The objective of this phase I clinical trial was to establish pairwise similarity between BAT1706, US-sourced BEV (US-BEV), and EU-sourced BEV (EU-BEV) after a single intravenous (IV) infusion in healthy male subjects. Methods This phase I clinical trial was a randomized, double-blinded, three-arm study in 128 healthy adult male subjects. Every subject received a single IV infusion of 1 mg/kg of study drug and was subsequently monitored for 14 weeks. Pharmacokinetic, safety, and immunogenicity data were collected from each patient. The primary pharmacokinetic endpoint of this clinical study was area under the concentration curve from time zero to infinity (AUC 0–inf ). Biosimilarity of the study drugs was confirmed if the two-sided 90% confidence interval (CI) ratios of the geometric means for the three pairwise comparisons were contained within the range 80–125%. Other pharmacokinetic parameters including area under the concentration curve to time t (AUC 0– t ), maximum concentration of drug in plasma ( C max ), half-life ( t ½ ), and time to C max ( t max ) were also measured. Results The pharmacokinetic parameters were comparable for the three drug products evaluated. The 90% CI for the AUC 0–inf was 99–112% for BAT1706 versus EU-BEV, 97–110% for BAT1706 vs US-BEV and 92–104% for EU-BEV versus US-BEV comparisons, respectively, demonstrating biosimilarity. There were no significant adverse events attributable to BAT1706, as compared to EU-BEV and US-BEV. BAT1706 demonstrated a similar safety profile to EU-BEV and US-BEV. In addition, no anti-drug antibody positive result was reported for any subject included in the study. Conclusion In this study, BAT1706, a proposed biosimilar of BEV, was shown to be highly similar to EU-BEV and US-BEV in terms of pharmacokinetic equivalence, safety, and immunogenicity in healthy subjects after a single IV infusion. Trial Registration NCT03030430.