BACKGROUND: Trastuzumab (Herceptin(®)) is a humanized monoclonal antibody 
targeting the human epidermal growth factor receptor 2 (HER2) and is used in the 
treatment of HER2-overexpressing breast and gastric cancer. FTMB is being 
developed as a biosimilar of trastuzumab.
OBJECTIVE: In this combined dose-escalation and bioequivalence study of parallel 
design, the pharmacokinetic profile of FTMB was compared with Herceptin(®).
METHODS: Healthy male volunteers received single doses of 0.5, 1.5, 3.0 or 6.0 
mg/kg FTMB, or placebo, in consecutive dose-escalation cohorts to assess the 
safety profile. Thereafter, the 6 mg/kg cohort was expanded to establish 
bioequivalence between FTMB (Test) and Herceptin(®) (Reference) based on an 
acceptance interval of 80.0-125.0 %. In total, 118 subjects were enrolled in the 
study.
RESULT: The mean area under the concentration-time curve from time zero to 
infinity (AUC∞) was 1,609 µg·day/mL (Test) and 1,330 µg·day/mL (Reference). The 
log-transformed geometric mean Test/Reference (T/R) ratio for AUC∞ was 89.6 % 
(90 % confidence interval [CI] 85.1-94.4), demonstrating bioequivalence. For the 
secondary endpoint, the maximum concentration observed (Cmax), the geometric 
mean T/R ratio was 89.4 % (90 % CI 83.4-95.9). Non-linear, target-mediated 
pharmacokinetics were also observed. Adverse events other than the documented 
side effects of Herceptin(®) (fever, influenza-like illness, and fatigue) did 
not occur. No signs of cardiotoxicity were observed.
CONCLUSIONS: This bioequivalence study with a trastuzumab biosimilar in healthy 
male volunteers demonstrated bioequivalence of FTMB with Herceptin(®). FTMB was 
well tolerated in doses up to 6 mg/kg. Non-linear target elimination was also 
observed in the pharmacokinetic profile of trastuzumab.