BACKGROUND AND OBJECTIVES: Olaratumab is a recombinant human monoclonal antibody 
that binds to platelet-derived growth factor receptor-α (PDGFRα). In a 
randomized phase II study, olaratumab plus doxorubicin met its predefined 
primary endpoint for progression-free survival and achieved a highly significant 
improvement in overall survival versus doxorubicin alone in patients with 
advanced or metastatic soft tissue sarcoma (STS). In this study, we characterize 
the pharmacokinetics (PKs) of olaratumab in a cancer patient population.
METHODS: Olaratumab was tested at 15 or 20 mg/kg in four phase II studies (in 
patients with nonsmall cell lung cancer, glioblastoma multiforme, STS, and 
gastrointestinal stromal tumors) as a single agent or in combination with 
chemotherapy. PK sampling was performed to measure olaratumab serum levels. PK 
data were analyzed by nonlinear mixed-effect modeling techniques using NONMEM®.
RESULTS: The PKs of olaratumab were best described by a two-compartment PK model 
with linear clearance (CL). Patient body weight was found to have a significant 
effect on both CL and central volume of distribution (V 1), whereas tumor size 
significantly affected CL. A small subset of patients developed 
treatment-emergent anti-drug antibodies (TE-ADAs); however, TE-ADAs did not have 
any effect on CL or PK time course of olaratumab. There was no difference in the 
PKs of olaratumab between patients who received olaratumab as a single agent or 
in combination with chemotherapy.
CONCLUSION: The PKs of olaratumab were best described by a model with linear 
disposition. Patient body weight and tumor size were found to be significant 
covariates. The PKs of olaratumab were not affected by immunogenicity or 
chemotherapeutic agents.