Multinational phase 1 trial of vimseltinib for CSF1R inhibition in patients with advanced solid tumors or tenosynovial giant cell tumor

Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colony-stimulating factor 1 (CSF1) gene and overexpression of the CSF1 ligand. Surgery is the standard of care for most patients, but there are limited treatment options for patients with TGCT not amenable for surgery. Vimseltinib is an investigational, oral, switch-control TKI designed to inhibit the CSF1 receptor (CSF1R). A multinational phase 1 trial evaluated vimseltinib in patients with malignant solid tumors (n=37) or TGCT not amenable to surgery (n=32). Vimseltinib was well tolerated. There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. The recommended phase 2 dose was determined to be 30 mg twice weekly, and vimseltinib plasma exposure increased with the dose. In patients with TGCT, the median treatment duration was 25.1 months (range 0.7-46.9) and the objective response rate as assessed by independent radiological review using RECIST version 1.1 was 72%. The authors conclude that vimseltinib demonstrated long-term tolerability, manageable safety, dose-dependent exposure, and robust antitumor activity in patients with TGCT not amenable to surgery.