By William Elliott, MD, FACP, and James Chan, PharmD, PhD
The U.S. Food and Drug Administration has approved vimseltinib for the treatment of tenosynovial giant cell tumor (TGCT) for which surgical resection is not desirable. Vimseltinib is an oral switch-control tyrosine kinase inhibitor designed specifically to selectively inhibit colony-stimulating factor 1 receptor (CSF1R).1 The drug was given a priority review and is distributed by Deciphera Pharmaceuticals LLC as Romvimza.
Indications
Vimseltinib is indicated for the treatment of adult patients with symptomatic TGCT for which surgical resection will potentially cause worsening functional limitation or severe morbidity.1
Dosage
The recommended dose is 30 mg orally twice weekly with a minimum of 72 hours between doses.1 It may be taken with or without food. Dose reduction or discontinuation is recommended for severity of hepatotoxicity based in laboratory values (e.g., increase in aspartate transaminase [AST] and/or alanine transaminase [ALT], total bilirubin). The dose may be reduced to 20 mg or 14 mg twice weekly. Vimseltinib is available as 30-mg, 20-mg, and 14-mg capsules.
Potential Advantages
Vimseltinib is a highly selective CSFR1 inhibitor and provides an effective treatment option for TGCT in patients not amenable to surgery.2 It does not appear to have the same risk of hepatotoxicy as the first drug in the class, pexidartinib, and does not require enrollment in a risk evaluation and mitigation strategies (REMS) program.
Potential Disadvantages
Vimseltinib can cause grade-3 increases in AST (2%) and ALT (1%). Cases of serious and fatal liver injury have occurred with another drug that targets CSF1R (pexidartinib).1 However, this has not been observed with vimseltinib. Based on animal studies, vimseltinib can cause embryo-fetal toxicity. Females of reproductive potential and male partners should use effective contraception during treatment and for one month after the last dose.1
The 20-mg capsule contains Federal Food, Drug, and Cosmetic Act (FD&C)
yellow #5, and the 14-mg and 20-g capsules contain FD&C yellow #6, which can cause allergic reactions in certain susceptible individuals.1 Common adverse reactions (> 30%) include periorbital edema (60% vs. 21% for placebo), fatigue
(59% vs. 38% for placebo), peripheral edema (31% vs. 8% for placebo), face edema (31% vs. 8% for placebo), rash (47% vs. 5% for placebo), increased AST (92% vs. 11% for placebo), increased cholesterol (43% vs. 16% for placebo), and decreased neutrophils (31% vs. 3% for placebo). Vimseltinib is a P-glycoprotein, breast cancer resistance protein (BCRP) and organic cation transporter 2 inhibitor. Therefore, concomitant administration of substrates for these transporters should be avoided.
Comments
TGCT is caused by dysregulation of the CSF1 gene, leading to promotion of tumor growth. Vimseltinib binds the region of CSF1R, effectively “switching off” the gene.3,4 The efficacy of vimseltinib was evaluated in a Phase III, double-blind, randomized, placebo-controlled study (MOTION) in participants with TGCT with at least one lesion sized at least 2 cm and for whom surgical resection may cause worsening functional limitation or severe morbidity.1,2 The median age of study participants was 44 years (range, 20 to 78 years), 59% of participants were female, 65% of participants were white, and 74% of participants had prior surgery. The most common disease locations were knee (67%) and ankle (12%). Participants were randomized to vimseltinib (n = 83) or placebo (n = 40) for
24 weeks.
The primary endpoint was the overall response rate (i.e., complete or partial), assessed radiologically. Key secondary endpoints included active range of motion, patient-reported physical function, and worst pain response (defined as at least 30% improvement) without a 30% or greater increase in narcotic analgesic use. Overall response was 40% (5% complete, 35% partial) compared to 0% for placebo. Median duration of response (DOR) was not reached in the vimseltinib arm.5
Based on an additional six months of data 85% had a DOR ≥ 6 months and 58% ≥ 9 months. There were statistically significant improvements in active range of motion, patient-reported physical functioning, and patient-reported pain in the vimseltinib arm. Vinseltinib showed an average improvement of 18.4 percentage points in active range of motion, compared to 3.8 percentage points for placebo.4
Clinical Implications
TGCT is a rare, noncancerous (but locally aggressive) inflammatory disorder affecting the joint synovium, bursa, and tendon sheaths.3,4 CSF1 binds to CSFR1, causing tumor growth and inflammation. TGCT is not life threatening but may significantly affect quality of life. Surgery is the initial approach to treatment.4 However, not all tumors can be completely removed, and there is a high rate of rapid recurrence/relapse. Pexidartinib was approved for this indication in 2019 but it carries a box warning for hepatotoxicity and is available only through the Turalio REMS Program. Vimseltinib may offer an effective non-surgical option with manageable adverse reactions and drug interactions. The cost of a four-week supply is $26,128.
References
- Deciphera Pharmaceuticals LLC. Romvimza prescribing information. Revised February 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219304s000lbl.pdf
- Gelderblom H, Bhadri V, Stacchiotti S, et al. Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024;403(10445):2709-2719.
- Chan AS, Katiyar V, Dy P, Singh V. Updates on the treatment of tenosynovial giant cell tumor. Hematol Oncol Stem Cell Ther. 2023;16(4):307-315.
- Bernthal NM, Stern S, Blay J-Y. Vimseltinib versus a placebo in patients with tenosynovial giant cell tumor: A plain language summary of the MOTION phase 3 trial. Future Oncol. 2024;20(39):3183-3192.
- U.S. Food and Drug Administration. FDA approves vimseltinib for symptomatic tenosynovial giant cell tumor. Feb. 14, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vimseltinib-symptomatic-tenosynovial-giant-cell-tumor
The U.S. Food and Drug Administration has approved vimseltinib for the treatment of tenosynovial giant cell tumor for which surgical resection is not desirable.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content