A Randomized Phase I Study Comparing the Pharmacokinetics of HD201, a Trastuzumab Biosimilar, With European Union-sourced Herceptin.

Purpose: This first-in-human study of HD201 was designed to evaluate the pharmacokinetic (PK) equivalence between this biosimilar candidate and trastuzumab sourced in the European Union (EU-trastuzumab)*.

Methods: In this randomized, blinded, single-dose comparative PK study, healthy male subjects were randomized to receive a single 6 mg/kg IV dose of HD201 or EU-trastuzumab. The primary PK end point was AUC. Equivalence was determined by using the predefined margins of 0.8 to 1.25. Other PK parameters were included as secondary end points.

Findings: Baseline demographic characteristics for the 73 randomized subjects were similar across the 2 groups: median age 29 and 30 years old (ranges 19 - 45), median weight 78.6 and 81.7 kg (ranges 60.2 - 101). The 90% CIs for the geometric least squares mean of the AUC were included within the margins of 0.8 to 1.25. All other PK parameters were comparable for both HD201 and EU-trastuzumab. The proportions of subjects who experienced adverse events related to the study drug were 61.8% and 82.9% in the HD201 and EU-trastuzumab groups, respectively. The most frequently reported adverse events related to the study drug were infusion-related reactions. No subjects had positive results for antidrug antibodies after a single dose.

Implications: This study reported the PK equivalence between HD201 and EU-trastuzumab. HD201 was well tolerated with no safety concerns after single-dose administration in healthy male subjects. EudraCT No.: 2012-000805-56.