Pimicotinib (CSF1R inhibitor) sustains ~76% ORR and improves knee ROM/PF across TGCT sites

Pimicotinib is an oral, highly selective CSF-1 receptor (CSF1R) inhibitor evaluated in the global Phase 3 MANEUVER trial (NCT05804045) in symptomatic, unresectable TGCT; this analysis reports longer-term outcomes by tumor location among patients randomized to pimicotinib in Part 1 (n=63; 84.1% diffuse; 85.7% lower extremity; 52.4% knee), with median follow-up 14.3 months. Longer-term BIRC RECIST v1.1 ORR appeared consistent across subgroups: localized 87.5% (n=8) vs diffuse 75.5% (n=53); lower extremity 75.9% (n=54) vs upper extremity 77.8% (n=9); knee 75.8% (n=33) vs other sites 76.7% (n=30). Functional signals tracked with tumor shrinkage—knee ROM mean change was +8.9° by Week 49, and PROMIS-PF item scores improved from baseline to Week 49 in lower-extremity tasks (e.g., walk ≥15 min 3.9→4.6; stairs 3.3→4.2; stand 1 hour 2.9→3.7; bend/kneel/stoop 2.7→3.6); for context, the only US-approved systemic option pexidartinib (CSF1R TKI) delivered a 39% RECIST ORR at Week 25 vs 0% with placebo in ENLIVEN but carries clinically meaningful hepatotoxicity risk (boxed warning), which has limited its practical uptake despite efficacy.