MANEUVER expands treatment options for tenosynovial giant cell tumors

medwireNews: Pimicotinib achieved robust antitumor activity and was well tolerated by people with symptomatic, unresectable tenosynovial giant cell tumor (TGCT) enrolled in the phase 3 MANEUVER trial, report the investigators in The Lancet.

Treatment with the highly selective colony-stimulating factor-1 receptor (CSF-1R) inhibitor was also associated with “clinically meaningful improvements in TGCT-related functional limitations and symptom burden,” they add.

The team continues: “Pimicotinib expands treatment options in TGCT and provides an additional, targeted, systemic treatment for patients who are not amenable to surgery.”

Xiaohui Niu (Capital Medical University, Beijing, China) and co-workers explain that “CSF-1R is a validated therapeutic target for systemic TGCT treatment,” and CSF-1R tyrosine kinase inhibitors such as pexidartinib and vimseltinib “have transformed the treatment landscape of TGCT.”

But “there has been concern over the unfavourable risk–benefit profile of pexidartinib, particularly the risk for severe hepatotoxicity,” they say, hypothesizing that the greater selectivity of pimicotinib “might limit off-target activity that is often associated with unwanted side-effects.”

The double-blind trial, conducted at 40 specialist hospitals in Asia, Europe, and North America, included 94 patients with unresectable TGCT that was symptomatic as defined by patient-reported worst stiffness or worst pain of at least 4 on a scale of 0–10.

The participants (median age 40 years, 68% women) were randomly assigned to received either oral pimicotinib 50 mg once daily or placebo for 24 weeks.

The primary endpoint of objective response by blinded independent review as per RECIST (version 1.1) at 25 weeks was achieved by 54% of the 63 patients who received pimicotinib and 3% of the 31 who received placebo, a significant difference.

Furthermore, “[s]tatistically significant improvements in change from baseline for all clinical outcome assessments were seen with pimicotinib versus placebo at week 25,” say the researchers.

For instance, the least squares mean change from baseline for relative range of motion was 15.6 in the pimicotinib group compared with –0.1 in the placebo group, while for the worst stiffness numerical rating scale score, the least squares mean changes were a respective –3.0 and –0.6.

A manageable safety profile

Treatment-emergent adverse events (AEs) of grade 3 or 4 occurred in 35% of pimicotinib-treated patients and 3% of those given placebo. The most common events of this severity in the pimicotinib arm were increased blood creatine phosphokinase (13 vs 0%) and increased blood pressure (3 vs 0%).

AE-related dose reductions were needed by five (8%) patients in the pimicotinib group and none in the placebo group, and there was one discontinuation in the former group, due to grade 2 fatigue.

However, there were no fatal AEs in either treatment arm, and “no evidence of cholestatic liver toxicity or drug-induced liver injury, and no reports of skin or hair hypopigmentation,” highlight Niu and colleagues.

They say in conclusion that “the pivotal MANEUVER trial supports the use of pimicotinib as a highly selective, potent, convenient therapeutic option that provides early and robust tumour reduction, with a manageable safety profile, in a diverse population of adult patients with TGCT.”

Further research required

Writing in a linked commentary, Jean-Yves Blay (Centre Léon Bérard and Université Claude Bernard, Lyon, France) says that “[t]he study has several weaknesses, including the small number of patients enrolled, the limited racial diversity, and short follow-up.”

He acknowledges, however, that the findings do show “that pimicotinib is an active agent in the observation period in the trial population with inoperable TGCT.”

Blay stresses that “[a]n analysis with a longer follow-up will be important,” and in the absence of comparator trials, so will further research addressing “how to integrate pimicotinib and other CSF-1R tyrosine kinase inhibitors into the multidisciplinary management of TGCT.”

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Lancet 2026; doi:10.1016/S0140-6736(26)00137-6
Lancet 2026; doi:10.1016/S0140-6736(26)00368-5