lavengratinib

Lavengratinib (ABSK061) is a first-in-class, potent, and selective small molecule inhibitor of fibroblast growth factor receptors 2 and 3 (FGFR2 and FGFR3). Developed by Abbisko Therapeutics, it is designed to target aberrant FGFR signaling, which is implicated in the development and progression of various cancers. Unlike pan-FGFR inhibitors, lavengratinib's selectivity for FGFR2/3 aims to improve the therapeutic window by reducing off-target toxicities associated with FGFR1 inhibition, such as hyperphosphatemia. It has demonstrated clinical activity in patients with FGFR2/3-altered solid tumors, including cholangiocarcinoma, gastric cancer, and urothelial carcinoma. Research into acquired resistance has identified secondary kinase domain mutations (such as N549, L617, E565, and V564 in FGFR2, and M528I in FGFR3) and bypass signaling pathways (RTK/RAS and DDR) as primary drivers of disease progression.