A randomized, double-blind, single dose comparison of pharmacokinetics and safety of FKB238 with bevacizumab.

• DOI: 10.1200/jco.2017.35.15_suppl.e14007
• Publication Date: 2018-09-06T16:03:02Z
• Authors: Hidekuni Kaito; Frans van den Berg; Andrew Niewiarowski; Malcolm Boyce
• Keywords: Biosimilar; Bioequivalence

e14007 Background: Bevacizumab is a recombinant humanized monoclonal antibody that binds selectively to vascular endothelial growth factor-A (VEGF-A). was first approved for treatment of metastatic colon cancer under the brand name Avastin; it has since been treating various other cancers. FKB238 being developed as biosimilar Avastin. In this first-in-human study, safety, pharmacokinetics (PK) and immunogenicity were compared those branded Avastin from US EU market. Methods: Ninety nine healthy male subjects randomly assigned receive single 5 mg/kg intravenous infusion either Avastin, or in 1:1:1 ratio. Safety, PK (anti-drug antibodies - ADA) assessed up 99 days after infusion. Each parameter (AUC 0-inf AUC 0–t primary; C max t 1/2 secondary) analysed assess similarity between established if each 2 primary parameters, 90% confidence interval (CI) ratio geometric means said 3-way comparison falls within 0.80-1.25. Results: A total randomized 96 completed study. The CI LS all 3 comparisons (FKB238/EU FKB238/US Avastin/EU Avastin) 4 parameters entirely pre-defined equivalence margin (0.80-1.25). Overall, 81% experienced an adverse event (AE) (FKB238: 97.0%; Avastin: 76.5%; 71.9%). Most AEs mild moderate intensity (Grade 1 by CTCAE ver. 4); most common headache (16.2%), epistaxis (8.1%) fatigue (5.1%). There no serious AEs. All had negative ADA against study drug at their last visit. Conclusions: demonstrated FKB238, subjects. well tolerated, with three compounds showed comparable safety profile significant evidence propensity form ADAs. This results support further development proposed Clinical trial information: 163882.