Exposure-response (E-R) relationship of ramucirumab (RAM) from two global, randomized, double-blind, phase 3 studies of patients (Pts) with advanced second-line gastric cancer.

121 Background: We evaluated the E-R relationship of RAM in pts with advanced gastric cancer from the REGARD and RAINBOW trials. Methods: Pts received RAM (8 mg/kg) or placebo (PL) q2w in REGARD; or RAM (8 mg/kg) or PL q2w + paclitaxel (PAC) 80 mg/m2 on days 1, 8, and 15 (28-day cycle) in RAINBOW. Sparse pharmacokinetic (PK) samples were collected; a population PK analysis was conducted. A model-predicted minimum concentration after first RAM dose (Cmin,1) was used for correlation with efficacy and safety variables. Kaplan-Meier, Cox regression, and logistic regression analyses evaluated E-R relationships. Results: Analyses included 72 RAM and 35 PL pts from REGARD and 321 RAM+PAC and 335 PL+PAC pts from RAINBOW. Conclusions: Ram was safe and effective at 8 mg/kg q2w. Population PK suggests higher RAM exposures were associated with longer PFS and OS, better hazard ratios, and increased toxicity. Further studies to validate the PK model and evaluate RAM dosing are warranted. Multivariate Cox Regression Ana...