A randomized, single-blind, single-dose study evaluating the pharmacokinetic equivalence of proposed biosimilar ABP 980 and trastuzumab in healthy male subjects

PURPOSE: This study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 980 and trastuzumab in healthy males. METHODS: In this single-blind study, 157 healthy males were randomized 1:1:1 to a single 6 mg/kg intravenous infusion of ABP 980, FDA-licensed trastuzumab [trastuzumab (US)], or EU-authorized trastuzumab [trastuzumab (EU)]. Primary endpoints were area under the serum concentration–time curve from time 0 to infinity (AUC(inf)) and maximum observed serum concentration (C (max)). To establish equivalence, the geometric mean ratio (GMR) and 90% confidence interval (CI) for C (max) and AUC(inf) had to be within the equivalence criteria of 0.80–1.25. RESULTS: The GMRs and 90% CIs for C (max) and AUC(inf), respectively, were: 1.04 (0.99–1.08) and 1.06 (1.00–1.12) for ABP 980 versus trastuzumab (US); 0.99 (0.95–1.03) and 1.00 (0.95–1.06) for ABP 980 versus trastuzumab (EU); and 0.96 (0.92–1.00) and 0.95 (0.90–1.01) for trastuzumab (US) versus trastuzumab (EU). All comparisons were within the equivalence criteria of 0.80–1.25. Treatment-emergent adverse events (TEAEs) were reported in 84.0, 75.0, and 78.2 of subjects in the ABP 980, trastuzumab (US), and trastuzumab (EU) groups, respectively. There were no deaths or TEAEs leading to study discontinuation and no binding or neutralizing anti-drug anti-bodies were detected. CONCLUSIONS: This study demonstrated the PK similarity of ABP 980 to both trastuzumab (US) and trastuzumab (EU), and of trastuzumab (US) to trastuzumab (EU). No differences in safety and tolerability between treatments were noted; no subject tested positive for binding anti-bodies.