Employed by Genentech during their involvement in this study.
Population pharmacokinetic analysis from phase I and phase II studies of the humanized monovalent antibody, onartuzumab (MetMAb), in patients with advanced solid tumors
Article first published online: 7 AUG 2013
© 2013, The American College of Clinical Pharmacology
The Journal of Clinical Pharmacology
Volume 53, Issue 11, pages 1103–1111, November 2013
How to Cite
Xin, Y., Jin, D., Eppler, S., Damico-Beyer, L. A., Joshi, A., Davis, J. D., Kaur, S., Nijem, I., Bothos, J., Peterson, A., Patel, P. and Bai, S. (2013), Population pharmacokinetic analysis from phase I and phase II studies of the humanized monovalent antibody, onartuzumab (MetMAb), in patients with advanced solid tumors. Journal of Clinical Pharma, 53: 1103–1111. doi: 10.1002/jcph.148
- Issue published online: 5 OCT 2013
- Article first published online: 7 AUG 2013
- Manuscript Accepted: 2 JUL 2013
- Manuscript Received: 19 FEB 2013
- monovalent antibody;
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.