(P 422) EFFICACY WITH VIMSELTINIB IN PATIENTS (PTS) WITH TENOSYNOVIAL GIANT CELL TUMOR (TGCT) AND PRIOR COLONY-STIMULATING FACTOR 1 (CSF1) INHIBITOR THERAPY: A PHASE 2 CASE SERIES

Objective: Vimseltinib, an oral, switch-control inhibitor of the CSF1 receptor (CSF1R), is approved in the US for treatment of symptomatic TGCT not amenable to surgery. In the phase 2 expansion of a phase 1/2 study (NCT03069469), vimseltinib showed promising antitumor activity (best overall response [BOR] rate of 64% and 37% in pts with TGCT without [cohort A] and with [cohort B] prior anti-CSF1/CSF1R therapy, respectively), favorable safety, and clinically meaningful improvements in pt-reported outcomes regardless of prior therapy. Here, we report efficacy with vimseltinib in pts with prior pexidartinib or vimseltinib treatment.

Methods: Pts with symptomatic TGCT not amenable to surgery were enrolled in this multicenter, open-label, phase 1/2 trial. In cohort B of phase 2, pts with prior anti-CSF1/CSF1R therapy received vimseltinib 30 mg twice weekly (BIW) in 28-day cycles. Antitumor activity (by independent radiological review [IRR] or local assessment using RECIST v1.1) and treatment duration were assessed in pts who received prior pexidartinib or vimseltinib (data cutoff: Feb 22, 2025).

Results: Among 20 pts enrolled in cohort B, 16 received prior pexidartinib, and the BOR rate on vimseltinib was 40%. Median treatment duration was 10.0 months on pexidartinib and 21.8 months on vimseltinib. Reasons for pexidartinib discontinuation were not known for some pts. Two pts in cohort B had prior vimseltinib. One pt had vimseltinib 30 mg BIW in phase 1 of this study (3 cycles; BOR: stable disease [SD] by local assessment, no IRR available); ~2.5 yrs posttreatment, they received 38 cycles of vimseltinib in cohort B with a BOR of partial response by IRR. The second pt had vimseltinib in cohort A (9 cycles; BOR: SD by IRR), and ~1 yr posttreatment, had 9 cycles of vimseltinib in cohort B, achieving a BOR of SD by IRR. This pt discontinued vimseltinib and has maintained SD (last follow-up: wk 60). Most treatment-emergent adverse events were grade 1/2, with no evidence of cholestatic hepatotoxicity or drug-induced liver injury.

Conclusion: These results suggest that pts with TGCT not amenable to surgery can derive clinical benefit from resumption of anti-CSF1R therapy, even after discontinuing the same (vimseltinib) or a different inhibitor. Vimseltinib retreatment was well tolerated with a manageable safety profile, consistent with prior reports.