Exposure-response (E-R) analysis of rilotumumab (R, AMG 102) plus epirubicin/cisplatin/capecitabine (ECX) in patients (pts) with locally advanced or metastatic gastric or esophagogastric junction (G/EGJ) cancer.

2535 Background: R is an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor (HGF/SF), the only known MET receptor ligand. In a double-blind, placebo-controlled, phase 2 trial of 121 pts with G/EGJ cancer, R (7.5 or 15 mg/kg) + ECX showed trends for improved overall survival (OS) and progression-free survival (PFS) compared to ECX alone (placebo, P). Methods: E-R analyses were performed using pharmacokinetic (PK), biomarker, efficacy, and safety data. A population PK model was used to evaluate covariate effects (eg, demographics, ECX, and MET status) on R PK and predict individual R exposure (trough steady-state Cmin [C]). The effect of C on OS/PFS was evaluated with Kaplan-Meier estimates and Cox proportional hazards models. Covariate effects for OS/PFS were evaluated with multivariate analysis. The relationships between adverse events of interest (AEs), lab values, and C were analyzed with descriptive statistics and linear regression models. Results: R showed line...