Phase 1/1b futibatinib FGFR1–4 inhibitor + paclitaxel + ramucirumab VEGFR2 mAb in 2L gastroesophageal adenocarcinoma.

This Phase 1/1b, open-label dose-escalation/expansion study tests whether adding futibatinib (Lytgobi; an irreversible covalent FGFR1–4 tyrosine kinase inhibitor, from Taiho Oncology/Taiho Pharmaceutical) to the established paclitaxel + ramucirumab backbone can be delivered safely and define a recommended combination dose in second-line locally advanced/unresectable gastric, gastroesophageal junction, or esophageal adenocarcinoma. Patients receive ramucirumab (Eli Lilly) on days 1 and 15 and paclitaxel on days 1, 8, and 15, with futibatinib introduced starting day 8 of cycle 1, then daily thereafter on 28‑day cycles. The target population is HER2-negative, microsatellite-stable disease (a majority phenotype in gastric/GEJ cancer), where actionable FGFR pathway dependence is not universal, making this a biomarker-development as well as tolerability question. The key commercial/scientific angle is “vertical stacking” of anti-angiogenic therapy (ramucirumab) with chemotherapy plus FGFR blockade to potentially deepen response or delay resistance on a widely used second-line regimen. Today’s care after progression on first-line platinum/fluoropyrimidine-based therapy (often with immunotherapy depending on PD-L1/other factors) commonly becomes paclitaxel + ramucirumab or other sequential systemic options, and this trial explores whether targeted FGFR inhibition can improve what is otherwise a chemo–anti-VEGFR2 standard.