Expert Perspectives on TGCT and the Outcomes of the Phase 3 MANEUVER Study of Pimicotinib Presented at ASCO and ESMO 2025: A Podcast Discussion

Abstract

Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm that significantly impacts patients’ quality of life through pain and swelling of the affected joint, resulting in limited range of motion. TGCT is categorized into two radiographic subtypes (localized and diffuse), and while surgery remains the treatment mainstay of localized TGCT, diffuse TGCT is associated with high local recurrence and incomplete resection, sometimes necessitating systemic therapy. Targeting the CSF-1/CSF-1R axis has emerged as a validated therapeutic approach, with several agents approved or in development. The Phase 3 MANEUVER study evaluated pimicotinib, a novel CSF-1R inhibitor, in patients with unresectable TGCT. This randomized, double-blind, placebo-controlled global trial enrolled 94 patients across China, Europe, and North America. Participants received pimicotinib (n = 63) or placebo (n = 31) for 24 weeks, followed by an open-label extension. The primary endpoint was objective response rate (ORR) by RECIST v1.1 at Week 25. Pimicotinib demonstrated a significant ORR of 54.0% versus 3.2% with placebo (p < 0.0001), with early and durable tumor responses. Secondary endpoints, including ORR by BIRC based on tumor volume score and clinical outcome assessments (range of motion, pain, stiffness, and physical function), also showed marked improvements with pimicotinib. Results from a 24-week open-label follow-up period from primary analysis confirmed sustained efficacy and tolerability, with ORR rising to 76.2% and continued improvements in clinical outcomes. Pimicotinib treatment was generally well tolerated, with low incidence of treatment discontinuation (6.3%) due to TEAEs, and no evidence of cholestatic hepatotoxicity, drug-induced liver injury, or hair/skin hypopigmentation. These results highlight pimicotinib as an effective, once-daily, oral therapy for patients with TGCT not amenable to surgery, addressing unmet needs in this population. In this podcast article, the authors share their perspectives on current TGCT treatment, discuss the patient care journey in the US, and highlight the clinical significance of the MANEUVER study findings. Podcast, infographics and plain language summary available for this article [ https://doi.org/10.6084/m9.figshare.32938235 ].