Long-term efficacy, clinical outcomes, and safety of vimseltinib in patients with tenosynovial giant cell tumor: results from the MOTION phase 3 trial

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by colony-stimulating factor 1 (CSF1) gene dysregulation. Vimseltinib is an oral, switch-control tyrosine kinase inhibitor of the CSF1 receptor. In part 1 of the MOTION phase 3 trial, vimseltinib demonstrated statistically significant and clinically meaningful improvements in antitumor activity and clinical outcome assessments (COAs). Here, we report long-term results from MOTION in patients with >2 years of follow-up on study. PATIENTS AND METHODS: MOTION is a randomized, double-blind, placebo-controlled, phase 3 trial with double-blind (part 1; to week 25), open-label (part 2; weeks 25-49), and extension periods (NCT05059262). Eligible adult patients with histologically confirmed TGCT not amenable to surgery received vimseltinib 30 mg twice weekly. Efficacy was assessed by objective response rate (ORR) on study evaluated by independent radiological review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and Tumor Volume Score. COAs and safety were assessed. RESULTS: In total, 118 patients received vimseltinib during MOTION (randomized to vimseltinib, n = 83; crossover, n = 35), with 51% (60/118) remaining on treatment. ORR on study per RECIST v1.1 was 48% (40/83) for patients randomized to vimseltinib and 54% (19/35) for crossover. Patients in both groups experienced long-term improvements in COAs. The safety profile was consistent with prior reports, with no evidence of cholestatic hepatotoxicity or drug-induced liver injury. CONCLUSION: Vimseltinib continued to provide robust and durable antitumor activity and demonstrated long-term improvements in COAs, with manageable safety for the treatment of patients with TGCT not amenable to surgery.