A Phase 1 study evaluating AMG 337 in Asian patients with advanced solid tumors†

Abstract

AMG 337, a selective small-molecule MET inhibitor, was evaluated in Asian patients with advanced solid tumors. Eligible patients orally self-administered AMG 337; the initial dose of 150 mg once daily (QD) was escalated to 300 mg QD (modified 3+3+3 design). Treatment continued until disease progression, intolerability, or death. The primary endpoint was adverse events (AEs) and clinical abnormalities defined as dose-limiting toxicities (DLTs). Secondary endpoints included other AEs, pharmacokinetics and tumor response. Eleven patients were enrolled. No DLTs occurred. The most common treatment-emergent AEs were headache (73%) and nausea (45%). C max and AUC 0-24 exposures increased proportionally with dose; t 1/2 was comparable between groups; plasma accumulation was minimal over 28 days. One patient (150 mg) had partial response; one patient (300 mg) had stable disease. Safety, tolerability, pharmacokinetics and efficacy of AMG 337 in Asian patients were consistent with those observed in Western patient populations. The study was terminated early.

MET deletion is a frequent event in gastric/gastroesophageal junction/esophageal cancer: a cross-sectional analysis of gene status and signal distribution in 1,580 patients

“…The association between MET amplification and a poor disease prognosis has likewise been confirmed in a meta-analysis (23). Beside the disease prognostic characteristics, it has been suggested that MET amplification potentially possesses predictive properties in relation to Met-targeted therapy and, thereby could act as a companion or complementary diagnostic in relation to the tyrosine kinase inhibitors under development for treatment of G/GEJ/E cancer and other indications (13,15,(24)(25)(26). Available data suggest that treatment plans targeting both Met and Her2 (human epidermal growth factor receptor 2 gene product) may be beneficial.…”

“…The study included 1,580 formalin-fixed and paraffinembedded (FFPE) G/GEJ/E adenocarcinoma specimens consecutively collected from the screening population of an international multi-center phase II trial with the Met tyrosine kinase inhibitor AMG337 (Amgen) (25). The limited demographic and clinical data were collected in relation with the MET eligibility testing for inclusion in the clinical phase II study with AMG337.…”