Development of PF-05280014, a potential biosimilar to trastuzumab.

618 Background: Trastuzumab, a humanized recombinant monoclonal antibody, targets HER2 and is approved for treatment of HER2-overexpressing breast and gastric cancers. PF-05280014 is being developed as a potential biosimilar to trastuzumab. Similarity of PF-05280014 to trastuzumab sourced from the EU and US (trastuzumab-EU and -US) was assessed using structural and functional, nonclinical pharmacokinetic (PK) and tolerability, and clinical studies; the toxicity of PF-05280014 was also assessed. Methods: Structural similarity was determined by peptide mapping. Functional similarity was measured using an in vitro tumor cell growth inhibition assay. Comparative PK, tolerability, and anti-drug antibody (ADA) responses were evaluated in male CD-1 mice following a single dose; PK and toxicity of PF-05280014 alone were evaluated in CD-1 mice (both sexes) after 5 doses. In a phase I study, 105 healthy male volunteers received a single 6 mg/kg IV dose of PF-05280014, trastuzumab-EU, or trastuzumab-US. Drug concent...