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.