Deciphera Pharmaceuticals and Ono Pharmaceutical have announced compelling two-year efficacy and safety results from the Phase 3 MOTION study of vimseltinib (ROMVIMZA) in patients with tenosynovial giant cell tumor (TGCT), demonstrating sustained antitumor activity and a manageable safety profile. The data, presented at the 2025 European Society for Medical Oncology Congress in Berlin, reinforce vimseltinib's position as a treatment option for patients with inoperable TGCT.
Sustained Clinical Benefit Across Multiple Endpoints
The global Phase 3 MOTION study (NCT05059262) evaluated vimseltinib's long-term efficacy in 118 patients with TGCT where surgical removal was not feasible. The two-part study design included an initial 24-week placebo-controlled phase followed by open-label vimseltinib treatment for all participants.
With a data cutoff of February 22, 2025, the results showed that 51% of patients (60/118) remained on treatment after two years. Among the 83 patients initially randomized to vimseltinib, the objective response rate (ORR) per RECIST v1.1 was 48% (40/83), while the ORR per Tumor Volume Score (TVS) reached 81% (67/83). Notably, patients who crossed over from placebo to vimseltinib in Part 2 achieved similar response rates of 54% per RECIST v1.1 and 71% per TVS.
The median treatment duration was 23.6 months for patients initially randomized to vimseltinib and 19.1 months for those who crossed over from placebo. Importantly, the median duration of response had not been reached for either RECIST v1.1 or TVS criteria, indicating durable therapeutic benefit.
Favorable Safety Profile Maintained
Vimseltinib continued to demonstrate a manageable safety profile consistent with previous reports, with no new safety signals emerging during the extended follow-up period. Most treatment-emergent adverse events (TEAEs) were grade 1/2, and the incidence of grade 3/4 TEAEs was similar between the initial vimseltinib group and crossover patients.
The safety analysis revealed no new TEAEs occurring in ≥15% of patients and no new serious adverse events affecting more than one patient. Serum enzyme elevations, consistent with the known mechanism of CSF1R inhibition, showed no evidence of cholestatic hepatotoxicity or drug-induced liver injury.
Addressing Unmet Medical Need in Rare Tumor
TGCT represents a rare, locally aggressive neoplasm caused by dysregulation of the colony-stimulating factor 1 (CSF1) gene, leading to CSF1 overproduction and recruitment of CSF1R-positive inflammatory cells. The condition, also known as giant cell tumor of the tendon sheath or pigmented villonodular synovitis, causes debilitating pain, stiffness, and impaired mobility through damage to surrounding tissues and joint structures.
"These long-term Phase 3 MOTION results add to the established body of evidence supporting vimseltinib as a best-in-class treatment for TGCT," said Matthew L. Sherman, M.D., Chief Medical Officer of Deciphera. "TGCT often causes debilitating pain, stiffness and impaired mobility and these results demonstrate the durable benefit that vimseltinib can offer patients."
Mechanism and Regulatory Status
Vimseltinib is an oral, switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R using Deciphera's proprietary platform. The drug has received approval in the United States for adult patients with symptomatic TGCT where surgical resection would potentially cause worsening functional limitation or severe morbidity. In the European Union, vimseltinib is approved for adult patients with TGCT associated with clinically relevant physical function deterioration where surgical options have been exhausted or would induce unacceptable morbidity or disability.
The treatment addresses a significant unmet medical need, as surgical options remain limited for many patients, and tumors frequently recur, particularly in diffuse-type TGCT. For patients where surgery is not feasible or would result in significant functional impairment, systemic treatment options have historically been limited.
These two-year results from the MOTION study provide robust evidence supporting vimseltinib's role in managing this challenging rare tumor, offering patients a durable treatment option with an acceptable safety profile for long-term use.
