Using Pharmacokinetic and Pharmacodynamic Data in Early Decision Making Regarding Drug Development: A Phase I Clinical Trial Evaluating Tyrosine Kinase Inhibitor, AEE788

Abstract

Our pharmacodynamic-based study showed effective inhibition of EGFR, but not of VEGFR at tolerable AEE788 doses. Emax modeling integrated with biomarker data effectively guided real-time decision making in the early development of AEE788. Despite clinical activity, target inhibition of only EGFR led to discontinuation of further AEE788 development.