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

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