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Population pharmacokinetic analysis from phase I and phase II studies of the humanized monovalent antibody, onartuzumab (MetMAb), in patients with advanced solid tumors


Corresponding Author:

John D. Davis, PhD, Genentech, Inc., 1 DNA Way, MS 46-3A, South San Francisco, CA 94080, USA



Onartuzumab is a unique, humanized, monovalent (one-armed) monoclonal antibody (mAb) against the MET receptor. The intravenous (IV) pharmacokinetics (PK) of onartuzumab were investigated in a phase I study and a phase II study in recurrent non-small cell lung cancer (NSCLC) patients. The potential for drug–drug interaction (DDI) was assessed during co-administration of IV onartuzumab with oral erlotinib, by measuring the PK of both drugs. The concentration–time profiles of onartuzumab were adequately described using a two-compartment model with linear clearance (CL) at doses between 4 and 30 mg/kg. The estimates for CL, central compartment volume (V1), and median terminal half-life were 0.439 L/day, 2.77 L, and 13.4 days, respectively. Statistically significant covariates included creatinine clearance (CrCL) on clearance, weight and gender on V1, and weight on peripheral compartment volume (V2), but the clinical relevance of these covariates needs to be further evaluated. The current analysis did not indicate obvious DDI between onartuzumab and erlotinib. MET diagnostic status did not impact the exposure of either agent. Despite the slightly faster clearance compared with typical bivalent mAbs, the PK of onartuzumab support dosing regimens of 15 mg/kg every 3 weeks or doses equivalent to achieve the target minimum tumoristatic concentration in patients.