The U.S. Food and Drug Administration (FDA) has approved vimseltinib (Romvimza), a kinase inhibitor, for adults with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity.
MOTION Trial
Efficacy was evaluated in MOTION (ClinicalTrials.gov identifier NCT05059262), a double-blind, multicenter, randomized, placebo-controlled trial. Eligible patients had a confirmed diagnosis of TGCT with measurable disease (per Response Evaluation Criteria in Solid Tumors version 1.1) with at least one lesion having a minimum size of 2 cm.
Patients were randomly assigned 2:1 to receive placebo or vimseltinib at 30 mg twice weekly administered for 24 weeks during the double-blind period (Part 1). During the open-label period (Part 2), patients could continue vimseltinib and those receiving placebos could crossover to vimseltinib. Random assignment was stratified by tumor location (lower limb vs all other sites) and region (United States vs non–United States). A total of 123 patients were randomly assigned (83 to the vimseltinib arm and 40 to placebo) during Part 1.
The major efficacy outcome measure was overall response rate assessed by blinded independent radiological review at week 25. Overall response rate was 40% (95% confidence interval [CI] = 29%–51%) in the vimseltinib arm and 0% (95% CI = 0%–9%) in the placebo arm (P < .0001). Median duration of response was not reached in the vimseltinib arm, and based on an additional 6 months of follow-up, 28 responders (85%) had a duration of response lasting at least 6 months, and 19 (58%) had a duration of response lasting at least 9 months. The primary endpoint was supported by statistically significant improvements in active range of motion, patient-reported physical functioning, and patient-reported pain observed in the vimseltinib arm compared with the placebo arm at week 25.
The most common adverse reactions (occurring in ≥ 20% of patients), including laboratory abnormalities, were increased aspartate aminotransferase, periorbital edema, fatigue, rash, increased cholesterol, peripheral edema, face edema, decreased neutrophils, decreased leukocytes, pruritus, and increased alanine aminotransferase.
The recommended vimseltinib dose is 30 mg orally twice weekly, with a minimum of 72 hours between doses.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review.
