David Weinreich, Global Head of R&D and Chief Medical Officer for the Healthcare business of Merck
Merck, a leading science and technology company, today announced new two-year follow-up results from the Phase 3 MANEUVER study evaluating pimicotinib in patients with tenosynovial giant cell tumor (TGCT). The study showed that among patients initially randomized to pimicotinib, improvements in symptoms and joint function were observed as early as Week 5, sustained through two years, and continued to improve over time. Tumor responses remained robust[1] and durable,[2] and the safety profile was consistent with previous analyses. The findings are being presented today in the Sarcoma poster session at the European Society for Medical Oncology (ESMO) Congress 2026 (Presentation # 3747P).
“For people living with TGCT, the impact of the disease is often felt through persistent limitations in mobility, physical function and the ability to carry out everyday activities,” said Vinod Ravi, MD, MS, MBA, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, an investigator on the MANEUVER trial. “What is encouraging about these two-year findings is the consistency of improvements, not only in the durability of tumor response, but across the symptoms and functional outcomes that matter to patients. Together with the observed safety profile, these results provide important insight into the potential for pimicotinib to deliver meaningful benefit over time.”
The new analysis in patients initially randomized to pimicotinib found that at Week 97, mean changes from baseline were 19.6% in range of motion, -3.9 in stiffness (as measured by the Worst Stiffness Numeric Scale Rating), -3.1 in pain (as measured by the Brief Pain Inventory worst pain rating) and +7.4 in physical function (as measured by the patient-reported PROMIS-PF scale).
Tumor responses also remained robust[1] and durable[2] through two years. Objective Response Rate (ORR) by blinded independent review committee (BICR) per RECIST v1.1 was 76.2% (95% CI: 63.8, 86.0), remaining unchanged from the one-year analysis, while ORR per BIRC based on tumor volume score (TVS) increased from 74.6% at one year to 77.8% (95% CI: 65.5, 87.3) at two years. Median duration of response was not reached at the time of analysis, and median treatment duration was 22.6 months (range: 1.8-33.6 months) at the March 1, 2026 data cutoff. Fifty-four percent of patients initially randomized to pimicotinib remained on treatment at two years.
In MANEUVER, pimicotinib was well-tolerated, with no evidence of cholestatic hepatotoxicity or hair/skin hypopigmentation. During the randomized, double-blind treatment phase of the trial, treatment-emergent adverse events (TEAEs) leading to treatment discontinuation occurred in one patient (1.6%) treated with pimicotinib; TEAEs leading to dose reduction occurred in 7.9% (n=5) of pimicotinib-treated patients.
“These two-year findings add to the growing body of evidence from the MANEUVER study demonstrating the potential for pimicotinib to meaningfully address some of the burden of TGCT,” said David Weinreich, MD, MBA, Global Head of R&D and Chief Medical Officer for the Healthcare business of Merck. “The sustained improvements observed across symptoms, physical function and tumor control reinforce the potential of pimicotinib to address aspects of TGCT that can affect patients every day. These results add to our evolving understanding of the long-term benefit that pimicotinib may provide for people living with this debilitating rare tumor.”
TGCT is a rare, locally aggressive tumor occurring in or around the joints leading to progressive worsening of symptoms including pain and reduced mobility of the affected joint, significantly impacting physical function in what is typically an otherwise healthy and young adult population. Patient-reported experiences indicate that up to half of people with TGCT may initially receive an incorrect diagnosis, which can delay appropriate disease management.[3] If left untreated or in recurrent cases, TGCT may result in cumulative morbidity and irreversible damage to the bone, joint and surrounding tissues.
Pimicotinib was approved in China by the China National Medical Products Administration (NMPA) in December 2025 and in Canada by Health Canada in June 2026 for the treatment of adult patients with symptomatic TGCT. A regulatory application is currently under review by the U.S. Food and Drug Administration (FDA) and other regulatory agencies.
[1] 54% ORR as assessed by BIRC based on RECIST v1.1 at week 25 vs. 3% with placebo; p<0.0001.
[2] The majority (77%) of patients with response at 25 weeks maintained this clinical benefit after an additional 12 months of treatment.
[3] Stern S, et al. Localized and diffuse tenosynovial giant cell tumor: real-world results from a patient observational registry. Future Oncol. 2025;21(12):1501-1510.
