Vimseltinib (CSF1R switch-control inhibitor) delivers 64% ORR in surgery-ineligible TGCT, including post–CSF1/CSF1R-treated patients

Vimseltinib is an oral “switch-control” kinase inhibitor of CSF1R designed to blunt the CSF1-driven macrophage biology underlying tenosynovial giant cell tumor (TGCT). In the multicenter, open-label Phase 2 expansion of a Phase 1/2 trial (NCT03069469), adults with histologically confirmed TGCT not amenable to surgery received vimseltinib 30mg twice weekly; ORR was 64% in anti-CSF1/CSF1R–naïve patients (cohort A; 29/45; mean follow-up 23 months) and 37% in previously anti-CSF1/CSF1R–treated patients (cohort B; 7/19; mean follow-up 19 months). Most TEAEs were grade 1/2 with no evidence of cholestatic hepatotoxicity or drug-induced liver injury—an important differentiator vs pexidartinib (ENLIVEN) where ORR was 39% at week 25 and clinically meaningful cholestatic liver injury risk drove a boxed warning/REMS in the US—while patients also reported meaningful improvements in ROM, stiffness, function, health status, and pain (key outcomes in this locally aggressive, quality-of-life–limiting disease).