Tinengotinib

Tinengotinib is a type I multi-kinase inhibitor active against FGFR1-3, including the FGFR2 kinase-domain resistance mutations (N550, V565) that emerge after pemigatinib or futibatinib, plus VEGFR, Aurora and JAK kinases. It is aimed at FGFR-altered cholangiocarcinoma that has progressed on a prior FGFR inhibitor, a group with no approved targeted option. A phase 1/2 study in heavily pretreated patients, including after prior FGFR inhibitors, showed disease control with median PFS of about 5 to 6 months. The global phase 3 FIRST-308 trial randomises FGFR inhibitor-refractory patients to tinengotinib versus FOLFOX or FOLFIRI, primary endpoint PFS; the first US patient was dosed in 2025. Whether its broad kinase profile adds toxicity without benefit over selective FGFR2 inhibitors is open. For a newcomer, it is a drug for bile duct cancer that has outgrown the existing FGFR pills.