Phase II study of AZD4547 in FGFR amplified tumours: Gastroesophageal cancer (GC) cohort pharmacodynamic and biomarker results.

154 Background: FGFR amplified tumors demonstrate oncogene addiction in vitro and in vivo. We examined the efficacy of AZD4547, an orally available inhibitor of FGFR 1, 2 & 3, in FGFR1/2 amplified cancers, and herein present results from a gastroesophageal cancer (GC) cohort. Methods: Phase II Simon 2 stage design (3 independent cohorts) for previously treated patients (pts) with advanced FGFR1 (HER2 negative breast/NSCLC) or FGFR2 amplified tumors. FGFR1/2 amplification was centrally assessed using FISH. Pts received AZD4547 80mg twice daily. Primary endpoint is centrally confirmed response rate (RR), with the study concluding efficacy if ≥ 3/17 patients in a cohort had a confirmed response. PET-CT was performed at baseline, D14 and 8 wks, biopsy at baseline and D14 and optionally on progression. Biomarkers included FGFR copy number variation in tumor and plasma, NanoString gene expression, MIRAX digital FISH imaging and phospho-immunohistochemistry. Results: Of 288 pts with screening results, 9% (12/138...