Vimseltinib for patients with tenosynovial giant cell tumor: A multicenter, open‐label, phase 2 trial

Vollständiger Abstract

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Abstract Background Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colony‐stimulating factor 1 ( CSF1 ) gene. Patients report substantial pain, stiffness, and declining physical function; those whose disease is not amenable to surgery require systemic therapy. Vimseltinib is an oral, switch‐control kinase inhibitor of the CSF1 receptor (CSF1R). Here, the authors report safety and efficacy of vimseltinib in patients with TGCT based on prior treatment. Cohort A included patients who did not receive prior specific anti‐CSF1/CSF1R agents ( n = 46; prior imatinib/nilotinib allowed), and cohort B included patients who received prior specific agents ( n = 20). Methods The phase 2 (expansion) portion of this ongoing, multicenter, open‐label, phase 1/2 study (NCT03069469) enrolled adults (≥18 years) with histologically‐confirmed TGCT not amenable to surgery. Patients received vimseltinib 30 mg twice weekly (recommended phase 2 dose). The primary objectives were to assess safety and antitumor activity; secondary objectives included assessment of active range of motion (ROM) and patient‐reported outcomes. Results Most treatment‐emergent adverse events were grade 1/2, and there was no evidence of cholestatic hepatotoxicity or drug‐induced liver injury. Best overall response rates were 64% (29 of 45) and 37% (7 of 19) for cohorts A and B after mean follow‐up of 23 and 19 months, respectively. Most patients experienced meaningful improvements in active ROM and patient‐reported physical function, stiffness, health status, and pain. Conclusions Vimseltinib had a manageable safety profile, demonstrated durable antitumor activity, and provided functional and symptomatic improvements in patients with TGCT, offering an effective treatment option regardless of previous treatment with anti‐CSF1/CSF1R agents.