EU Approval Sought for Vimseltinib in Tenosynovial Giant Cell Tumor

The European Medicines Agency has accepted the marketing authorization application (MAA) seeking the approval of vimseltinib for use as a therapeutic option in patients with tenosynovial giant cell tumor (TGCT).¹

The MAA is based on findings from the phase 3 MOTION study (NCT05059262) in which the investigational, oral, switch-control TKI designed to inhibit CSF1R (n = 83) elicited an objective response rate (ORR) of 40% at week 25 by RECIST 1.1 criteria vs 0% with placebo (n = 40) in this population (P < .0001).² The median duration of response (DOR) had not yet been reached (NR; range, 0.03+ to 11.7+) with vimseltinib.

“Building upon positive results from the MOTION pivotal phase 3 study, we are excited to initiate the regulatory review process in the European Union and we are one step closer in our mission to bring vimseltinib to TGCT patients in need of an effective and well-tolerated treatment,” Steve Hoerter, president and chief executive officer of Deciphera Pharmaceuticals, stated in a news release.¹

The international, randomized, double-blind, placebo-controlled, phase 3 study enrolled patients with a confirm diagnosis of symptomatic TGCT for which surgical resection would potentially cause worsening functional limitation or severe morbidity.² They were required to be at least 18 years of age, and they were allowed to have prior exposure to imatinib (Gleevec) or nilotinib (Tasigna).

For the double-blind period of the study, eligible patients were randomly assigned 2:1 to receive vimseltinib at a twice-daily dose of 30 mg or matching placebo for 24 weeks. Randomization was stratified by geographical region and tumor location. The study also has an open-label period in which participants in both arms have the option to continue treatment, or if on the placebo arm, to cross over to receive vimseltinib.

The study’s primary end point was ORR by independent radiological review (IRR) and RECIST 1.1 criteria at week 25. The secondary end points hierarchy is as follows: IRR-assessed ORR using tumor volume score (TVS), change from baseline in active range of motion, and patient-reported outcomes—specifically change from baseline in physical function, worst stiffness numeric rating scale, health status, and Brief Pain Inventory worst pain response rate.

The median patient age in the vimseltinib arm was 45 years (range, 33-53) vs 42 years (range, 31-53) in the placebo arm. Most patients in both arms were female (55%; 68%), White (71%; 53%), and previously underwent TGCT surgery or procedure (77%; 68%). Joints affected in the vimseltinib arm included knee (67%), ankle (11%), hip (13%), and other (8%); in the placebo arm, these respective percentages were 68%, 15%, 3%, and 15%. In the vimseltinib arm, 19% received prior imatinib, 2% had prior nilotinib, and 1% had another treatment; these respective rates were 18%, 10%, and 0% in the placebo arm.

Additional data showed that the ORR with vimseltinib using TVS was 67% vs 0% with placebo (P < .0001). The median DOR was NR (range, 0.03+ to 13.9+).

Vimseltinib treatment led to statistically significant and clinically meaningful improvements in active range of motion (18.4% vs 3.8%; percentage difference, 14.6%; P = .0077), PROMIS-Physical function (mean change, 4.6 vs 1.3; difference, 3.3%; P = .0007), worst stiffness Numeric Rating Scale (mean change, -2.1 vs -0.3; difference, -1.8%; P < .0001), EQ-Visual Analogue Scale (mean change, 13.5 vs 6.1; difference, 7.4%; P = .0155), and Brief Pain Inventory (40% vs 9%; percentage difference, 26%; P = .0056).

Notably, approximately 40% of patients who received vimseltinib experienced a response in at least 3 clinical outcomes vs 6% of those who were given placebo, irrespective of ORR by IRR using RECIST 1.1 criteria.

Regarding safety, vimseltinib was generally well tolerated. The most common treatment-emergent adverse effects (TEAEs) experienced with the agent included periorbital edema (all grade, 45%; grade 3/4, 4%), fatigue (33%; 0%), face edema (31%; 1%), pruritus (29%; 2%), headache (28%; 1%), asthenia (27%; 1%), nausea (25%; 0%), increased blood creatine phosphokinase (24%; 10%), increased aspartate aminotransferase (23%; 0%), arthralgia (19%; 0%), rash (19%; 0%), maculopapular rash (19%; 1%), peripheral edema (18%; 0%), hypertension (17%; 5%), and diarrhea (12%; 0%).

No instances of cholestatic hepatotoxicity, drug-associated liver injury, or hair/skin hypopigmentation were observed.

Six percent of patients experienced TEAEs that resulted in treatment discontinuation.

References

1. European Medicines Agency accepts Deciphera’s marketing authorization application for vimseltinib for treatment of patients with tenosynovial giant cell tumor (TGCT). News release. Ono Pharmaceutical, Ltd. July 19, 2024. Accessed July 19, 2024. https://www.ono-pharma.com/en/news/20240719.html
2. Tap WD, 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):11500. doi:10.1200/JCO.2024.42.16_suppl.11500