Efficacy, safety, and patient-reported outcomes of vimseltinib in patients with tenosynovial giant cell tumor: Results from the phase 3 MOTION trial.

11500 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. TGCT requires a therapy with low toxicity as patients (pts) may need long-term treatment; there is an unmet need for an effective, well-tolerated CSF1 receptor (CSF1R)-targeted therapy that improves functional health and quality of life (QoL). Vimseltinib is an investigational, oral, switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R. Here we report results from the MOTION trial. Methods: MOTION is a global, phase 3, double-blind study of vimseltinib in pts with symptomatic TGCT not amenable to surgery (NCT05059262). Randomization was 2:1 to vimseltinib 30 mg twice weekly or matching placebo (pbo) for 24 weeks. The primary endpoint was objective response rate (ORR) assessed by blinded independent radiological review (IRR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) at week 25. Key secondary endpoints assessed at week 25 were ORR by IRR per tumor volume score (TVS), change from baseline in active range of motion (ROM) of the affected joint and patient-reported outcomes (PROs; PRO Measurement Information System physical function score [PROMIS-PF], worst stiffness numeric rating scale, and EuroQol Visual Analog Scale [EQ-VAS]), and brief pain inventory worst pain response. Safety was also evaluated. Data cutoff was August 22, 2023. Results: Overall, 123 pts were randomized to vimseltinib (n = 83) or pbo (n = 40). Median age was 44 years, 59% of pts were female, and the most common primary disease location was the knee (67%). ORR at week 25 by IRR per RECIST v1.1 and per TVS were significantly higher for vimseltinib vs pbo (RECIST: 40% vs 0%, P < 0.0001; TVS: 67% vs 0%; P < 0.0001). Significant improvements from baseline to week 25 were observed with vimseltinib vs pbo in active ROM (18.4% vs 3.8%; P = 0.0077), physical function (PROMIS-PF: 3.3-point difference between arms, P = 0.0007), worst stiffness (−1.8-point difference, P < 0.0001), and health status (EQ-VAS: 7.4-point difference, P = 0.0155). There were also significantly more pain responders treated with vimseltinib (48% vs 23%; P = 0.0056). Most non-laboratory treatment-emergent adverse events were grade 1/2, and there was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. Conclusions: Patients treated with vimseltinib experienced statistically significant and clinically meaningful improvements in ORR by RECIST v1.1 and by TVS, active ROM, physical function, stiffness, health status, and pain vs pbo. Vimseltinib is an effective, well-tolerated CSF1R-targeted therapy that demonstrates significant clinical benefit and improves functional health and QoL in pts with symptomatic TGCT not amenable to surgery. Clinical trial information: NCT05059262 .