Onartuzumab (MetMAb): Using Nonclinical Pharmacokinetic and Concentration–Effect Data to Support Clinical Development

Abstract

Onartuzumab pharmacokinetics differed from typical bivalent glycosylated monoclonal antibodies with approximately 2-times faster CL in the linear dose range. Despite this higher CL, xenograft efficacy data supported dose flexibility with Q1W to Q3W dose regimens in the clinical setting with a TSC of 15 μg/mL as the Ctrough ss target. The projected human efficacious dose of 10 to 30 mg/kg Q3W should achieve the target TSC of 15 μg/mL. These data show effective pharmacokinetic/pharmacodynamic modeling to project doses to be tested in the clinic.