FDA Approves Vimseltinib for Symptomatic Tenosynovial Giant Cell Tumor

The FDA has approved vimseltinib (Romvimza) for the treatment of patients with symptomatic tenosynovial giant cell tumor (TGCT) for whom surgical resection will potentially cause worsening functional limitation or severe morbidity.1

This regulatory decision was supported by findings from the phase 3 MOTION trial (NCT05059262), in which vimseltinib elicited a 40% (95% CI, 29%-51%) overall response rate (ORR) at week 25 vs 0% (95% CI, 0%-9%) with placebo in the intent-to-treat (ITT) population (difference, 40%; 95% CI, 29%-51%; P < .0001).1,2 The median duration of response (DOR) was not reached with vimseltinib. At an additional 6 months of follow-up, 85% of responders had achieved a DOR of at least 6 months, and 58% of responders had a DOR of at least 9 months.

"We're very excited to have vimseltinib recently approved," William Tap, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, said in an interview with OncLive®. "TGCT, especially the diffuse type, can be a very devastating disease for people. It's not something that generally threatens their life, but it can really alter the trajectory of their life. People live with the disease for long periods of time and can have tremendous symptoms and a lot of disability from it, so to have medical options for TGCT is critical for us."

The multicenter, double-blind MOTION trial enrolled patients at least 18 years of age with histologically confirmed TGCT for which surgical resection might worsen functional limitations or cause severe morbidity.

Between January 21, 2022, and February 21, 2023, 123 patients were randomly assigned 2:1 to receive vimseltinib at 30 mg orally twice weekly (n = 83) or placebo (n = 40), each given in 28-day cycles for 24 weeks.

ORR at week 25 assessed by independent radiological review (IRR) per RECIST 1.1 criteria in the ITT population served as the primary end point. Secondary end points included ORR by IRR per tumor volume score (TVS), change from baseline in active range of motion (ROM) of the affected joint, change from baseline in TGCT-specific Patient-Reported Outcomes Measurement Information System physical function (PROMIS-PF), worst stiffness numeric rating scale (NRS), EuroQoL Visual Analogue Scale (EQ-VAS) health status, and Brief Pain Inventory (BPI) worst pain response rate.

Additional findings from the study, which were presented at the 2024 ASCO Annual Meeting and concurrently published in The Lancet, showed that treatment with vimseltinib led to a statistically significant ORR advantage over placebo in almost every prespecified patient subgroup. Furthermore, 95% of patients in the vimseltinib arm experienced a decrease in tumor size per RECIST criteria. At a data cutoff date of August 22, 2023, the median duration of response (DOR) for patients who achieved an objective tumor response at week 25 was not reached (range, 0.03 months-11.7 months).

The ORR by IRR per tumor volume score at week 25 was also significantly higher in the vimseltinib arm vs the placebo arm, at 67% vs 0% (difference, 67%; 95% CI, 56%-77%; P < .0001). In total, 5% and 63% of patients in the vimseltinib arm had a CR and PR, respectively, per TVS. The median DOR by IRR per TVS was NR (range, 0.03 months-13.9 months).

The least squares (LS) mean change in active ROM from baseline in the affected joint at week 25 was significantly higher in the vimseltinib arm vs the placebo arm, at 18.4% (standard error [SE], 6.5) vs 3.8% (SE, 7.2), respectively (difference, 14.6%; 95% CI, 4.0-25.3; P = .0077). Significant improvements in physical function, as measured by PROMIS-PF, were also noted with vimseltinib vs placebo (LS mean change from baseline difference, 3.3; 95% CI, 1.4-5.2; P = .0007). The PROMIS-PF response rates were 43% and 25% in these respective arms (difference, 18%; 95% CI, 1%-36%; P = .046).

Treatment with vimseltinib also significantly improved stiffness, inducing an LS mean change from baseline of –2.1 (SE, 0.2) vs –0.3 (SE, 0.3) with placebo (difference, –1.8; 95% CI, –2.5 to –1.1; P < .0001). The worst stiffness NRS response rates were 39% and 15%, respectively (difference, 24%; 95% CI, 8%-39%; P = .008).

The EQ-VAS response rate was numerically higher in the vimseltinib arm, at 37% vs 25% in the placebo arm, although this difference was not statistically significant (difference, 12%; 95% CI, –5% to 29%; P = .16). The LS mean change in EQ-VAS from baseline was 13.5 (SE, 2.4) in the vimseltinib arm vs 6.1 (SE, 2.9) in the placebo arm (difference, 7.4; 95% CI, 1.4-13.4; P = .016). The BPI worst pain response rates were 48% and 23% in these respective arms (difference, 26%; 95% CI, 4%-42%; P = .0056).

Grade 3 or 4 treatment-emergent adverse effects (TEAEs) occurred in 37% of patients in the vimseltinib safety population (n = 83) vs 10% of those in the placebo safety population (n = 40). The most common TEAEs reported in the vimseltinib arm were periorbital edema (any-grade, 45%; grade 3/4, 4%), fatigue (33%; 0%), facial edema (31%; 1%), pruritus (29%; 2%), headache (28%; 1%), asthenia (27%; 1%), nausea (25%; 0%), increased blood CPK levels (24%; 10%), and increased aspartate aminotransferase levels (23%; 0%).

Grade 3 or 4 treatment-related AEs occurred in 30% of patients in the vimseltinib arm vs 3% of those in the placebo arm.

Notably, investigators did not observe evidence of cholestatic hepatotoxicity or drug-induced liver injury.

References

1. FDA approves vimseltinib for symptomatic tenosynovial giant cell tumor. 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. 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. doi:10.1016/S0140-6736(24)00885-7