Pimicotinib Versus Placebo for Tenosynovial Giant Cell Tumour (MANEUVER): An International, Randomised, Placebo-Controlled, Phase 3 Trial

Authors

Hairong Xu
Xiaohui Niu
Vinod Ravi
Javier Martin-Broto
Albiruni Abdul Razak
Ramy Saleh
Yong Zhou
Jingnan Shen
Tang Liu
Kamlesh Kumar Sankhala
César Serrano
Silvia Stacchiotti
Jing Wang
Giacomo G Baldi
Yi Feng
Yingqi Hua
Tao Li
Piotr Rutkowski
Xiaojing Zhang
Gabriel Tinoco
Qingping Zou
Boyao Shan
Xiangyu Zhu
Hans Gelderblom

Language

English

Publication Date

3-14-2026

Journal

Lancet

DOI

10.1016/S0140-6736(25)02602-9

PMID

41796601

Abstract

Background: Tenosynovial giant cell tumour (TGCT) is a rare, locally aggressive neoplasm that affects otherwise healthy adults. There are few systemic treatment options, highlighting an unmet need. We report the results of part 1 of the MANEUVER trial, which aimed to evaluate the efficacy and safety of pimicotinib, a highly selective, potent, colony-stimulating factor-1 receptor inhibitor, in patients with TGCT.

Methods: MANEUVER is a randomised, placebo-controlled, phase 3 study done in 40 specialised hospitals in Asia, Europe, and North America. Patients aged 18 years and older with unresectable, symptomatic TGCT (patient-reported worse stiffness or worst pain of at least 4 on a scale of 0-10) were randomly assigned (2:1, double-blind) to oral, once-daily pimicotinib 50 mg or placebo for 24 weeks (part 1). An independent statistician used a central interactive web response system to generate the randomisation schedule; stratification was by region (China vs non-China). Masking was achieved by using placebo identical in appearance to pimicotinib. In part 1, patients, all investigators, and study funders were masked to treatment assignments. All patients who completed part 1 were allowed to continue to open-label part 2: pimicotinib-treated patients could continue the same dosage and placebo-treated patients could cross over to receive pimicotinib for 24 weeks. Eligible patients who completed part 2 were allowed to continue once-daily pimicotinib long-term in part 3. The primary endpoint was objective response rate (ORR) at week 25 by blinded independent review committee per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population (all randomised patients). Safety was analysed in patients who received at least one dose of study drug. Missing data were not imputed and only observed data were analysed. Trial enrolment is complete; the study is registered at ClinicalTrials.gov (NCT05804045) and is ongoing.

Findings: Between April 27, 2023, and March 29, 2024, 126 patients were screened and 94 patients (China [n=45], non-China [n=49]) were randomly assigned to, and received, pimicotinib (n=63) or placebo (n=31). 30 (32%) patients were male and 64 (68%) were female. ORR at week 25 was 54% (34 of 63) in the pimicotinib group and 3% (one of 31) in the placebo group (absolute difference 51% [95% CI 33-63], p< 0·0001). Pimicotinib was associated with mainly mild treatment-emergent adverse events, including mostly manageable asymptomatic laboratory abnormalities and clinical events, such as pruritus, facial oedema, rash, periorbital oedema, and fatigue. The only grade 3 or 4 treatment-emergent adverse event occurring in more than 10% of pimicotinib-treated patients was increase in blood creatine phosphokinase, in eight (13%) of 63 patients. The most common treatment-emergent adverse events in the placebo group were fatigue and arthralgia. Dose reductions occurred in five (8%) of 63 pimicotinib-treated patients and treatment discontinuations in one (2%) of 63 pimicotinib-treated patients. There was no cholestatic hepatotoxicity, drug-induced liver injury, or hypopigmentation of skin or hair.

Interpretation: Pimicotinib showed robust antitumour activity with clinically meaningful improvements in TGCT-related functional limitations and symptom burden, offering an effective treatment option with a manageable safety profile for this underserved condition.

Funding: Abbisko Therapeutics.

Keywords

Adult, Female, Humans, Male, Middle Aged, Antineoplastic Agents, Double-Blind Method, Giant Cell Tumor of Tendon Sheath, Treatment Outcome, Receptors, Colony-Stimulating Factor, Receptor Protein-Tyrosine Kinases

Published Open-Access

yes

Recommended Citation

Xu, Hairong; Niu, Xiaohui; Ravi, Vinod; et al., "Pimicotinib Versus Placebo for Tenosynovial Giant Cell Tumour (MANEUVER): An International, Randomised, Placebo-Controlled, Phase 3 Trial" (2026). Faculty, Staff and Student Publications. 6638.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6638