741TiPRILOMET-1: AN INTERNATIONAL PHASE 3 MULTICENTER RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL OF RILOTUMUMAB PLUS EPIRUBICIN, CISPLATIN AND CAPECITABINE (ECX) AS FIRST LINE THERAPY IN PATIENTS WITH ADVANCED MET-POSITIVE GASTRIC OR GASTROESOPHAGEAL JUNCTION (G/GEJ) ADENOCARCINOMA

Abstract Background: Rilotumumab is an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor that inhibits signaling through the MET receptor. In a randomized phase 2 study in patients with advanced G/GEJ adenocarcinoma, addition of rilotumumab every 3 weeks (Q3W) to ECX showed trends toward improved overall survival (OS; 10.6 vs 8.9 months; hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.45–1.09) and progression-free survival (PFS; 5.7 vs 4.2 months; HR, 0.60; 95% CI, 0.39–0.91) vs ECX alone. In patients with high tumor MET expression, the treatment effect of rilotumumab combined with ECX was significantly enhanced (median OS, 10.6 vs 5.7 months; HR, 0.46; 95% CI, 0.24–0.87). Trial design: In this phase 3 study, patients (planned N = 600) are randomized 1:1 to ECX (intravenous [IV] epirubicin 50 mg/m2 on day 1, IV cisplatin 60 mg/m2 on day 1, and oral capecitabine 625 mg/m2 twice daily on days 1–21) plus double-blind rilotumumab 15 mg/kg or placebo IV Q3W. Randomization is stratified by disease extent (locally advanced vs metastatic) and Eastern Cooperative Oncology Group (ECOG) score (0 vs 1). Key eligibility criteria include previously untreated, pathologically confirmed unresectable locally advanced or metastatic G/GEJ adenocarcinoma; ECOG score 0 or 1; ≥18 years old; MET-positive by centralized immunohistochemistry; HER2-negative; adequate organ function; and ≥6 months since neoadjuvant/adjuvant therapy. The primary endpoint is OS. Key secondary endpoints include PFS, 12-month survival rate, objective response, safety, and pharmacokinetics. An exploratory objective is to assess associations between outcomes and tumor and circulating biomarkers. Enrollment began in November 2012, and the trial continues to accrue in the North and South Americas, Europe, and Australia. An independent data monitoring committee will conduct planned interim reviews for safety and efficacy. Status: recruiting participants. Sponsored by Amgen Inc.; ClinicalTrials.gov: NCT01697072. This abstract was accepted and presented at the 2013 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois, USA (abstract number: TPS4153; citation: J Clin Oncol 31, 2013 [suppl; abstr TPS4153]). Disclosure: D. Cunningham: is a consultant/advisor for Roche and Amgen Inc. and received research funding from Roche, Amgen Inc., Celgene, Sanofi Aventis, Merck Serono, and Novartis; S. Al-Batran: is a consultant/advisor for and received re