Phase III, randomized, double-blind, multicenter, placebo (P)-controlled trial of rilotumumab (R) plus epirubicin, cisplatin and capecitabine (ECX) as first-line therapy in patients (pts) with advanced MET-positive (pos) gastric or gastroesophageal junction (G/GEJ) cancer: RILOMET-1 study.

Abstract

4000 Background: R is a fully human monoclonal antibody to hepatocyte growth factor. A phase 2 study showed improved overall survival (OS) and progression-free survival (PFS) with R + ECX vs P + ECX in MET-pos G/GEJ cancer (Lancet Oncol 2014;15:1007). This phase 3 trial evaluated the efficacy and safety of R + ECX in MET-pos G/GEJ cancer. Methods: Key eligibility criteria: ≥ 18 yr; previously untreated, pathologically confirmed unresectable advanced G/GEJ adenocarcinoma; ECOG score 0–1; tumor MET-pos by IHC; HER2-negative. Pts were randomized 1:1 to receive ECX (IV epirubicin 50 mg/m2 D1, IV cisplatin 60 mg/m2 D1, oral capecitabine 625 mg/m2BID D1−21) + R 15 mg/kg or P IV Q3W and stratified by disease extent (locally advanced vs metastatic) and ECOG score (0 vs 1). Primary endpoint: OS. A log-rank test stratified by randomization factors compared OS between arms. The study was powered to detect a HR of 0.69. Key secondary endpoints: PFS, 12-mo survival rate, objective response rate (ORR), safety and pharmacokinetics (PK). Results: 609 pts were randomized from Nov 2012 to Nov 2014. The study was stopped early based on an imbalance in deaths (R vs P: 128 vs 107 deaths, data cutoff: 27 Nov 2014). R was not superior to P for OS (one-sided test, p = 0.99). OS, PFS and ORR were statistically worse in the R arm. No subgroups seemed to benefit with R, including those with higher percentages of cells with ≥ 1+ MET expression. Most common AEs that were higher with R: peripheral edema, hypoalbuminemia, deep vein thrombosis and hypocalcemia. Conclusions: RILOMET-1 did not meet its primary endpoint; OS was statistically significantly worse with R. PK and MET biomarker analyses are pending. Clinical trial information: NCT01697072. R (n = 304) P (n = 305) R vs P Median OS,* mo 9.6 (7.9–11.4) 11.5 (9.7–13.1) HR†= 1.37 (1.06–1.78) p = 0.016 Median PFS,* mo 5.7 (5.3–5.9) 5.7 (5.5–7.1) HR†= 1.30 (1.05–1.62) p = 0.016 12-mo survival rate* 38.4% (30.2%–46.6%) 49.7% (41.5%–57.4%) Diff = -11.4 (-22.9–0.2) p = 0.053 ORR* 30% (24.6%–36.0%) 39.2% (33.3%–45.4%) Odds ratio = 0.67 (0.46–0.96) p = 0.027 *95% CI shown. †Stratified.