Evaluation of MET pathway biomarkers in a phase II study of rilotumumab (R, AMG 102) or placebo (P) in combination with epirubicin, cisplatin, and capecitabine (ECX) in patients (pts) with locally advanced or metastatic gastric (G) or esophagogastric junction (EGJ) cancer.

• DOI: 10.1200/jco.2012.30.15_suppl.4005
• Publication Date: 2020-03-11T19:13:37Z
• Authors: Kelly S. Oliner; Rui Tang; Abraham Anderson; Yun Lan; Timothy Iveson; Ross C. Donehower; Yizhou Jiang; Sarita Dubey; Elwyn Loh
• Keywords: Epirubicin

4005 Background: R is an investigational, fully human, monoclonal antibody to HGF/SF, the ligand of MET receptor. A double-blind, P-controlled, phase 2 study randomized 121 G/EGJ cancer pts 1:1:1 15 mg/kg + ECX (Arm A, n = 40), 7.5 B, 42), or P C, 39). OS and PFS improved with addition (Iveson et al, European Multidisciplinary Cancer Congress 2011; abstr 6.504). High tumor levels have been associated poor prognosis in G (Nakajima 1999;85:1894-1902). We explored pathway biomarkers identify who may benefit from R. Methods: protein gene copy numbers were measured archival samples by immunohistochemistry (IHC) fluorescence situ hybridization, respectively. low subgroups defined several predefined strategies. Total HGF soluble (sMET) plasma ELISA MSD assays, Treatment biomarker effects on analyzed Cox proportional hazard models Kaplan-Meier estimates. Results: Tumor evaluable for 62 Arms B 28 Arm C. Pts tumors (> 50% cells positive) had median than those C (11.1 mo [80% CI: 9.2-13.3] vs 5.7 4.5-10.4]; HR 0.29, 95% 0.11-0.76, p 0.012). Conversely, Low (≤ a trend toward unfavorable compared (HR 1.84, 0.78-4.34). In chemotherapy only arm C), poorer 3.22, 1.08-9.63) tumors. Similar trends seen PFS. Predefined dichotomization schemes number baseline total sMET did not correlate Conclusions: expression IHC predict clinical pts. also be ECX-treated Further investigation needed confirm these findings.