Vimseltinib Gains FDA Approval in Tenosynovial Giant Cell Tumor

• The FDA has approved vimseltinib (DCC-3014) for the treatment of symptomatic tenosynovial giant cell tumor (TGCT).
• This regulatory decision is supported by data from the phase 3 MOTION study (NCT05059262).
• The primary end point of objective response rate at week 25 was met at 40% (95% CI, 29%-51%) for patients with TGCT not amenable to surgery who were treated with vimseltinib.

The FDA has granted approval to vimseltinib, a colony stimulating factor 1 receptor (CSF1R), for the treatment of patients with symptomatic TGCT.¹

Data from the phase 3, 2-part, randomized, double-blind, placebo-controlled MOTION study support this regulatory decision, and at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, efficacy, safety, and patient-reported outcome data were presented. The study randomly assigned patients in a 2:1 fashion to receive 30 mg of vimseltinib twice weekly or placebo for 25 weeks.

At week 25, the overall response rate (ORR) by RECIST v1.1 was 40% (95% CI, 29%-51%; P <.0001) among patients treated with vimseltinib vs 0% among those given placebo. The ORR included 4 (5%) complete responses, 29 (35%) partial responses, and 42 (51%) cases of stable disease.² Additionally, the median duration of response (DOR) was not reached with vimseltinib (range, 0.03-11.7+), and the ORRs by tumor volume score were 67% (95% CI, 56%-77%; P <.0001) with vimseltinib vs 0% with placebo.

Statistically significant and clinically meaningful improvements were also seen among those given vimseltinib vs placebo such as active range of motion, physical function, stiffness, and pain. Regardless of tumor response, about 40% of patients treated with vimseltinib had a response in 3 or more clinical outcomes compared with 6% of those given placebo.

For safety, most treatment-emergent adverse events (TEAEs) were deemed to be grade 1 or 2. The most common any-grade TEAEs observed in the vimseltinib arm were periorbital edema (45%), fatigue (33%), face edema (31%), pruritus (29%), headache (28%), asthenia (27%), nausea (25%), increased creatinine (24%), and increased aspartate aminotransferase (23%).

Serum enzyme elevations were consistent with the known mechanisms of CSF1R inhibitors. Further, no observations of cholestatic hepatotoxicity, drug-induced liver injury, or hypopigmentation of the hair or skin were noted.

The recommended vimseltinib dose is 30 mg orally twice weekly, with a minimum of 72 hours between doses.¹

REFERENCES:

1. FDA approves vimseltinib for symptomatic tenosynovial giant cell tumor. News release. FDA. February 14, 2025. Accessed February 14, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vimseltinib-symptomatic-tenosynovial-giant-cell-tumor

2. Tap W, Bhadri V, Stacchiotti S, et al. Efficacy, safety, and patient-reported outcomes of vimseltinib in patients with tenosynovial giant cell tumor: results from the phase 3 MOTION trial. J Clin Oncol. 2024;42(suppl 16):abstr 11500. doi:10.1200/JCO.2024.42.16_suppl.11500)