Population pharmacokinetic analysis of patritumab, a HER3 inhibitor, in subjects with advanced non-small cell lung cancer (NSCLC) or solid tumors.

Abstract

The purpose of this analysis was to develop a population pharmacokinetic (PK) model for patritumab, a fully human monoclonal antibody that targets human epidermal growth factor receptor 3. A total of 833 serum concentrations were included in this analysis; serum concentrations were obtained from 145 subjects (136 with non-small cell lung cancer, nine with solid tumors) treated with patritumab [9 or 18mg/kg intravenously every 3weeks (q3w)] in one phase 1 and one phase 1b/2 study. Data were analyzed by nonlinear mixed-effect modeling. Patritumab PKs were best described through a two-compartment model with first-order elimination and interindividual variability on clearance (CL), volume of the central compartment (V c), distributional clearance, and volume of the peripheral compartment. In the final model, CL and V c were estimated as 0.0238L/h and 3.62L, respectively. Body weight (BW) and baseline albumin were found to be covariates for CL and BW was a covariate for V c. Covariates associated with hepatic and renal impairment were not significant on CL. Simulations showed that BW-based dosing reduced interindividual variability in patritumab exposure compared with fixed dosing. The PK of patritumab was linear at the doses studied and well described by the two-compartment model. Hepatic and renal impairment did not appear to affect PK. Our results support BW-based dosing of patritumab on a q3w schedule.