AIMS: Rilotumumab is a fully human monoclonal antibody investigated for the 
treatment of MET-positive gastric cancer. The aim of this study was to evaluate 
the potential pharmacokinetic (PK)-based drug-drug interaction (DDI) between 
rilotumumab and epirubicin (E), cisplatin(C) and capecitabine (X).
METHODS: This was a Phase 3 double-blind, placebo-controlled study, in which 
rilotumumab, epirubicin and cisplatin were administered intravenously at 
15 mg kg-1 , 50 mg m-2 , and 60 mg m-2 Q3W, respectively, while capecitabine was 
given orally at 625 mg m-2 twice daily. Rilotumumab PK samples were taken at 
pre-dose and at the end-of-infusion from all patients in cycles 1, 3, 5 and 7. 
ECX PK samples were taken in cycle 3 from patients who participated in the 
intensive PK assessment. ECX PK was assessed by non-compartmental (NCA) analyses 
and PK parameters were compared between two arms. Rilotumumab PK was assessed by 
comparing the observed rilotumumab serum concentrations with model-predicted 
concentrations using a population PK model developed from previous Phase 1 and 
Phase 2 studies.
RESULTS: The study enrolled 609 patients. ECX plasma concentrations in the 
presence and absence of rilotumumab were similar, as demonstrated by the 
geometric mean ratios for Cmax and AUC, which were close to 1.0, suggesting ECX 
PK was not affected by co-administration of rilotumumab. The observed 
rilotumumab serum concentrations were similar to the values predicted by 
population PK modelling on the basis of a prediction-corrected visual predictive 
check, indicating rilotumumab exposure was not affected by co-administration of 
ECX.
CONCLUSIONS: The results suggest lack of PK-based DDI between rilotumumab and 
ECX.