The study demonstrated pharmacokinetic similarity of FKB327 with EU- and US-Humira. FKB327 was well tolerated by healthy subjects, with adverse effects similar to Humira. If clinical similarity to Humira, including efficacy, can be shown in patients, FKB327 will meet the criteria for biosimilarity to Humira.

Background: BT1718 is a novel bicyclic peptide anticancer drug targeting membrane type I matrix metalloproteinase to release its toxic payload DM1. A LC–MS/MS method was validated to quantify DM1 generated from BT1718 in a Phase I/IIa clinical trial. Materials & methods: Plasma samples underwent a reduction reaction to artificially cleave BT1718 into DM1 and its bicycle components. An alkylation step was carried out to stabilize the reaction products, and plasma proteins extracted using acetonitrile. LC–MS/MS analysis utilized a C18 column and Agilent 6460 triple quadrupole mass spectrometer (Agilent, Cheshire, UK). Results: The method was fully validated over a linear range of 200–50,000 ng/ml BT1718, with overall precision ≤10% and accuracy 89–102%. Conclusion: A novel method for quantifying DM1 yielded from BT1718 has been validated and is now being utilized clinically.

No abstract

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 (AUC0-inf and AUC0–t as primary; Cmax and t1/2 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.