FIRST-308

FIRST-308, sponsored by TransThera, is the first phase 3 trial for patients whose bile duct cancer has outgrown the existing FGFR drugs, testing tinengotinib against FOLFOX or FOLFIRI chemotherapy in FGFR-altered cholangiocarcinoma refractory to chemotherapy and a first-generation FGFR inhibitor. It is a global randomised trial with progression-free survival as the primary endpoint, and the first US patient was dosed in 2025. OnCo links it to biliary tract cancer, FGFR2 as a target and tinengotinib. Whether a next-generation inhibitor active against kinase-domain resistance mutations can beat chemotherapy in patients who have already progressed on targeted therapy is the question it exists to answer.