Abstract OT1-1-05: A Phase I pharmacokinetics trial comparing PF-05280014 and trastuzumab in healthy volunteers (REFLECTIONS B327-01)

Abstract

Abstract Background: Trastuzumab is a humanized recombinant monoclonal antibody that selectively binds the extracellular domain of human epidermal growth factor receptor 2 (HER2) and is approved for treatment of breast and gastric cancers. PF05280014 is being developed as a potential biosimilar to trastuzumab. In nonclinical evaluations, PF-05280014 has an identical amino acid sequence to trastuzumab and similar physicochemical and in vitro functional properties. The goal of this phase I trial is to demonstrate the pharmacokinetic similarity of PF-05280014 to trastuzumab sourced from both the United States (trastuzumab-US) and European Union (trastuzumab-EU). Trial design: In this double-blind, parallel group, single dose trial, subjects will be randomized 1:1:1 into 3 arms: PF-05280014; trastuzumab-US, and trastuzumab-EU (NCT01603264). Eligibility: Healthy male volunteers, 18–55 years of age with normal left ventricular ejection fraction are eligible. Multiple exclusion criteria common to Phase 1 trials are in effect. All subjects must provide informed consent. Aims: The primary objectives are to demonstrate the pharmacokinetic similarity of PF-05280014 to trastuzumab-US and trastuzumab-EU. Secondary objectives include evaluating the safety, tolerability, and immunogenicity of PF-05280014 compared with US-licensed and EU-approved trastuzumab products. Statistical methods: Pharmacokinetic similarity will be demonstrated if the 90% confidence interval of the ratio of the area under the concentration-versus-time curve from time 0 to the last time point with quantifiable concentration (AUCT) and maximum concentration (Cmax) of PF-05280014 to both trastuzumab-US and trastuzumab-EU are within 80%–125%. At least 93 subjects, 31/arm, will be needed to provide >81% power to demonstrate pharmacokinetic similarity for all comparisons. The planned enrolment is 105 subjects to account for subjects who may not complete the full follow-up period. The intent-to-treat (ITT) population is defined as all subjects who are randomized to receive treatment. The modified ITT population is defined as all subjects who are randomized and receive at least one dose of treatment and will be used to assess safety, tolerability, and immunogenicity. The per-protocol population is defined as all subjects who are randomized to and receive treatment and do not have any major protocol violations and will be used for the primary evaluation of pharmacokinetic parameters. Accrual: The target accrual is 105 subjects; present accrual is 17subjects. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT1-1-05.