Long-term clinical outcome assessments in patients with tenosynovial giant cell tumor treated with vimseltinib: 1-year results from the MOTION phase 3 trial.

11558 Background: Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colony-stimulating factor 1 ( CSF1 ) gene leading to overproduction of CSF1. Patients with TGCT often report substantial pain and stiffness, impaired physical function, and limited range of motion (ROM), supporting the need for an effective, well-tolerated CSF1 receptor (CSF1R)-targeted therapy that provides long-term improvements in functional health and quality of life (QoL). Vimseltinib is an oral, switch-control inhibitor of CSF1R. In part 1 of the MOTION phase 3 trial, vimseltinib showed statistically significant and clinically meaningful improvements vs placebo in tumor response as well as clinical outcome assessments (COAs; active ROM and patient-reported outcomes [PROs]) in patients with TGCT not amenable to surgery at week 25 (Gelderblom H, et al. Lancet . 2024). Here we report 1-year COA results from MOTION. Methods: MOTION is a global, phase 3 trial composed of double-blind (part 1; to week 25), open-label (part 2; week 25–49), and extension periods (NCT05059262). Patients received vimseltinib 30 mg twice weekly. COAs reported here include change from baseline in active ROM of the affected joint, physical function (PRO Measurement Information System physical function score [PROMIS-PF]), stiffness (worst stiffness numeric rating scale [NRS]), health status (EuroQol Visual Analog Scale [EQ-VAS]), and pain (brief pain inventory [BPI] worst pain). BPI worst pain response rate is also reported with response defined as ≥30% decrease in worst pain without ≥30% increase in narcotic analgesic use. Results are reported in patients randomized to vimseltinib during part 1 whose 1-year (week-49) assessments were complete at data cutoff (Feb 22, 2024). Results: Of 83 patients randomized to vimseltinib in part 1, 73 continued treatment in the open-label part of the study. Consistent with results from part 1, COAs at 1 year continued to show improvement from baseline. Mean (standard error [SE]) change from baseline in active ROM was 14.9 (5.0) percentage points. Mean (SE) changes from baseline in PROMIS-PF, worst stiffness NRS, and EQ-VAS were 6.5 (1.2), −2.7 (0.4), and 11.0 (3.5) points, respectively. Mean (SE) change from baseline in BPI worst pain was −2.8 (0.4) points, and the BPI worst pain response rate was 40% (33/83; 95% confidence interval, 29 to 51). Conclusions: These 1-year COA results from the MOTION phase 3 trial demonstrate durable and continued improvements in active ROM, physical function, stiffness, health status, and pain with ongoing vimseltinib treatment. Continued treatment with vimseltinib provides clinically meaningful benefit in functional health and QoL beyond week 25 for patients with symptomatic TGCT whose disease is not amenable to surgery. Clinical trial information: NCT05059262 .