A target‐mediated drug disposition population pharmacokinetic model of GC1118, a novel anti‐EGFR antibody, in patients with solid tumors

ABSTRACT: GC1118 is a monoclonal antibody for epidermal growth factor receptor (EGFR) that is currently under clinical development to treat patients with solid tumors. In this study, the pharmacokinetics (PKs) of GC1118 were modeled in solid tumor patients who received a 2‐h intravenous infusion of GC1118 at 0.3, 1, 3, 5, or 4 mg/kg once‐weekly (Q1W) on days 1, 8, 15, and 22 or 8 mg/kg every other week on days 1 and 15. A target‐mediated drug disposition population PK model adequately described the concentration‐time profiles of GC1118. Monte‐Carlo simulation experiments of the PK profiles and EGFR occupancies (ROs) by GC1118 based on the final model showed that Q1W at 4 or 5 mg/kg will produce a better antitumor effect than Q2W at 8 mg/kg. Because GC1118 was safer at 4 mg/kg than 5 mg/kg in the phase I study, we suggest to test the 4 mg/kg Q1W regimen in further clinical trials with GC1118. STUDY HIGHLIGHTS: WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? GC1118, a fully human IgG(1) WHAT QUESTION DID THIS STUDY ADDRESS? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? The pharmacometrics analysis could support better informed drug development decisions for GC1118, particularly for determining an optimal dosage regimen.