Multinational placebo-controlled phase 3 trial of pimicotinib for tenosynovial giant cell tumor

There are few systemic treatment options for tenosynovial giant cell tumor (TGCT). The phase 3 MANEUVER trial, at 40 centers on Asia, Europe, and North America, evaluated the colony-stimulating factor-1 receptor inhibitor pimicotinib for TGCT. Patients aged 18 years or older with unresectable, symptomatic TGCT were randomized 2:1 to pimicotinib 50 mg (n=63) once daily or placebo (n=31) for 24 weeks. The primary endpoint was objective response rate at week 25 by blinded independent review committee. The objective response rate at week 25 was 54% in the pimicotinib group versus 3% in the placebo group (p<0.0001). Pimicotinib was associated with mainly mild treatment-emergent adverse events; the only grade 3 or 4 TRAE occurring in more than 10% of pimicotinib-treated patients was increased blood creatine phosphokinase (13% or patients). Dose reductions occurred in five (8%) of pimicotinib-treated patients and treatment discontinuation in one (2%). There was no cholestatic hepatotoxicity, drug-induced liver injury, or hypopigmentation of skin or hair. The authors conclude that pimicotinib showed robust antitumor efficacy with clinically meaningful improvements in TGCT-related functional limitations and symptom burden, offering an effective treatment option with a manageable safety profile.