ESMO 2025: Vimseltinib Demonstrates Statistically Significant and Clinically Meaningful Benefit in Patients Diagnosed with Tenosynovial Giant Cell Tumor

A two-year efficacy and safety results from its MOTION Phase 3 study (NCT05059262) of vimseltinib (Romvimza™; Deciphera/Ono Pharmaceutical Co.), a kinase inhibitor, in patients with Tenosynovial Giant Cell Tumor (TGCT) in cases where surgical removal of the tumor is not an option were presented as a poster during the 2025 European Society for Medical Oncology Congress (ESMO), taking place October 17-21 in Berlin, Germany.

Vimseltinib was approved by the U.S. Food and Drug Administration on February 14, 2025, for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity.

TGCT is caused by a dysregulation in colony-stimulating factor 1 (CSF1) gene leading to overproduction of CSF1 and recruitment of colony-stimulating factor 1 receptor (CSF1R)-positive inflammatory cells into the lesion.[1]

TGCT is also known as giant cell tumor of the tendon sheath (GCT-TS) or pigmented villonodular synovitis (PVNS). TGCT is a rare, locally aggressive neoplasm that can grow and cause damage to surrounding tissues and structures, inducing pain, swelling, and limitation of movement of the joint.

Surgery is the main treatment option; however, these tumors tend to recur, particularly in diffuse-type TGCT. If untreated or if the cancer continually recurs, damage and degeneration may occur in the affected joint and surrounding tissues, which may cause significant disability. For a subset of patients, surgical resection will potentially cause worsening functional limitation or severe morbidity. Systemic treatment options are limited, and new therapeutic options are needed.[1][2]

Vimseltinib is an oral, switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R, and has been developed using Deciphera’s proprietary switch-control kinase inhibitor platform. It has been approved in the United States for adult patients with symptomatic TGCT for which surgical resection will potentially cause worsening functional limitation or severe morbidity, and in the European Union for adult patients with TGCT associated with clinically relevant physical function deterioration and in whom surgical options have been exhausted or would induce unacceptable morbidity or disability.

Trial results
“These long-term Phase 3 MOTION results add to the established body of evidence supporting vimseltinib as a best-in-class treatment for TGCT,” noted 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,” Sherman added.

The global Phase 3 MOTION study evaluated the efficacy and safety of vimseltinib for the treatment of TGCT in cases where surgical removal of the tumor is not an option.

The study consisted of two parts: an eligible study (Part 1) where participants were randomly assigned to receive either vimseltinib 20 mg twice weekly or a matching placebo for 24 weeks. Participants assigned to placebo in Part 1 had the option to cross over and receive vimseltinib during the open-label part (Part 2) of the study.

Part 2 was a long-term treatment phase in which all participants received open-label vimseltinib. Patients received vimseltinib 30 mg twice weekly in all periods. Objective response rate (ORR) based on best overall response was assessed by independent radiological review (IRR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and per Tumor Volume Score (TVS). Duration of response (DOR) and safety were also evaluated.

In these two-year results from the MOTION Phase 3 trial, vimseltinib continued to demonstrate robust and durable antitumor efficacy with a manageable safety profile that was consistent with prior reports. These long-term results support vimseltinib as a treatment option for patients with TGCT associated with clinically relevant physical function deterioration and in whom surgical options have been exhausted or would induce unacceptable morbidity or disability, where it is approved. These results are reported with two years of follow-up in patients randomized to vimseltinib in Part 1 and crossed over from placebo to vimseltinib in Part 2.

Trial design
In total, 118 patients received vimseltinib. At data cutoff (February 22, 2025), 51% (60/118) remained on treatment. With at least 2 years of follow-up, results demonstrate robust and durable antitumor activity with vimseltinib per RECIST v1.1 and per TVS, including in patients who crossed over to vimseltinib in Part 2.

• A total of 83 patients were randomized to vimseltinib in Part 1, and 73 continued open-label treatment in Part 2. Median (range) treatment duration was 23.6 months (2 to 36).
• 40 patients randomized to placebo in Part 1, 35 crossed over to vimseltinib in Part 2. Median treatment duration for this group was 19.1 months (1 to 30).
• ORR on study per RECIST v1.1 was 48% (40/83) for patients randomized to vimseltinib and 54% (19/35) for those who crossed over to vimseltinib. ORR on study per TVS was 81% (67/83) for patients randomized to vimseltinib and 71% (25/35) for those who crossed over to vimseltinib.
• The corresponding median DOR per RECIST v1.1 and per TVS was still not reached.

Safety
Vimseltinib continued to have a manageable safety profile that was consistent with prior reports, with no new safety signals.

• Most treatment-emergent adverse events (TEAEs; ≥20%) included laboratory abnormalities, as well as increased aspartate aminotransferase, periorbital edema, fatigue, rash, increased cholesterol, peripheral edema, face edema, decreased neutrophils, decreased leukocytes, pruritus, and increased alanine aminotransferase.
• These TEAWs were grade 1/2, and grade 3/4 TEAEs were similar between randomized vimseltinib and crossover groups.
• There were no new TEAEs in ≥15% of patients receiving vimseltinib and no new serious adverse events in more than one patient.
• Serum enzyme elevations were consistent with the known mechanism of action of CSF1R inhibition, and there was no evidence of cholestatic hepatotoxicity or drug-induced liver injury.

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Clinical trials
Study of Vimseltinib for Tenosynovial Giant Cell Tumor (MOTION) – ClinicalTrials.gov ID NCT05059262

Highlights of prescribing information
Vimseltinib (Romvimza™; Deciphera/Ono Pharmaceutical Co.)[Prescribing Information]

Reference
[1] 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
[2] Stacchiotti S, Dürr HR, Schaefer IM, et al. Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts. Cancer Treat Rev. 2023;112:102491. doi:10.1016/j.ctrv.2022.102491

Featured image: European Society for Medical Oncology (ESMO) Asia Congress 2019, held November 22 – 24, 2019, in Singapore. Photo Courtesy: ESMO. Used with permission.

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