FDA Approves Vimseltinib in Tenosynovial Giant Cell Tumor

Vimseltinib elicited an ORR of 40% vs 0% of matching placebo in patients with tenosynovial giant cell tumor in the phase 3 MOTION trial.

The FDA has approved vimseltinib (Romvimza), a kinase inhibitor, in the treatment of patients with tenosynovial giant cell tumor (TGCT), in which surgical resection may cause worsening functional limitation or severe morbidity according to a press release from the FDA.¹

The double-blind, randomized phase 3 MOTION trial (NCT05059262) that evaluated the efficacy of vimseltinib in patients with TGCT who did not have the option for surgical removal of the tumor informed the FDA’s decision.²

The recommended dose of vimseltinib is 30 mg twice weekly for 24 weeks. The open-label portion is where patients could cross over to the treatment arm.

In August 2024, the new drug application was granted priority review by the FDA and a Prescription Drug User Fee Act date of February 17, 2025 was set.³

The objective response rate (ORR) per RECIST in the vimseltinib group was 40% (n = 33/83) vs 0% (n = 0/40) in the placebo group (difference 40%; 95% CI, 29%-51%); P <.0001). Of patients in the vimseltinib group (n=83), 4 (5%) had a complete response (CR), 29 (35%) had a partial response (PR), 42 (51%) had stable disease (SD), and 8 (10%) were not evaluable (NE).

Regarding safety, treatment-emergent adverse effects (TEAEs) of grade 3 or 4 occurred in 37% of patients in the vimseltinib group and 10% of patients in the placebo group; 1 patient and 0 patients in the vimseltinib group and placebo group, respectively, experienced a treatment-related serious TEAE. The most common TEAEs of grade 3 or 4 in the vimseltinib group were increased blood CPK (10%), hypertension (5%), periorbital oedema (4%), and pruritus (2%); in the placebo group, they were asthenia (3%), nausea (3%), arthralgia (3%), hypertension (3%), and diarrhea (3%).

The trial’s primary end point was ORR by independent radiological review (IRR) per RECIST. Secondary end points include ORR by IRR per tumor volume score; change from baseline in active range of motion of the affected joint as measured by goniometry assessments; change from baseline in Patient-Reported Outcomes Measurement Information System physical function (PROMIS-PF; TGCT specific), worst stiffness numeric rating scale, and EuroQOL Visual Analogue Scale health status; and Brief Pain Inventory worst pain response rate.

A total of 123 patients were randomly assigned, in a 2:1 ratio, to either the vimseltinib group or the placebo group. The median age was 44 years; the most common disease location was in the knee (67%) and 74% of patients had at least 1 prior surgery or procedure.

Patients were administered either 30 mg of vimseltinib or matching placebo administered orally twice weekly in 28-day cycles for 24 weeks. On days 1 and 5 of each week, at approximately the same time and on an empty stomach, vimseltinib was administered.

Inclusion criteria include an age of 18 years or older, histologically confirmed TGCT for which surgical resection would worsen functional limitation or cause severe morbidity, and at least 1 lesion measuring at least 2 cm in size. Having received prior systemic therapy targeting CSF1 or CSF1R, including vimseltinib, was grounds for exclusion.

References

1. FDA approves vimseltinib for symptomatic tenosynovial giant cell tumor. News release. FDA. February 14, 2025. Accessed February 14, 2025. https://tinyurl.com/5n8ryu5f
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
3. U.S. Food and Drug Administration accepts for priority review Deciphera’s new drug application for vimseltinib for the treatment of patients with tenosynovial giant cell tumor (TGCT). News release. Ono Pharmaceutical, Co., Ltd. August 16, 2024. Accessed August 16, 2024. https://tinyurl.com/25zn6b96