Key takeaways
Strong ORR validates trial design and execution: The trial achieved a 54% objective response rate vs. 3.2% for placebo, marking the highest ORR to date in systemic TGCT treatment. This highlights the robustness of the protocol, endpoints, and eligibility criteria—a validation point for clinical ops planning similar future trials in rare musculoskeletal tumors.
Comprehensive patient-reported outcomes strengthen value proposition: Statistically significant improvements in pain, stiffness, and range of motion were captured through secondary endpoints. Clinical ops teams should note the value of patient-reported outcomes (PROs) for capturing real-world impact, especially in quality-of-life-driven indications.
Efficient execution of multi-part global study: The three-part, global, randomized, double-blind design with a clear transition from placebo-controlled to open-label demonstrates scalable, phased trial structuring. Ops teams may take note of this as a model for balancing regulatory rigor and compassionate use in orphan indications.
Merck KGaA has announced it will be presenting positive results from the Phase III MANEUVER clinical trial of pimicotinib, an investigational colony stimulating factor-1 receptor (CSF-1R) inhibitor, in patients with tenosynovial giant cell tumor (TGCT). In the trial, once daily pimicotinib achieved a statistically significant improvement in objective response rate (ORR), meeting the primary endpoint. Data from MANEUVER will be presented at the upcoming American Society of Clinical Oncology (ASCO) meeting.1
Significant improvements in pain, mobility, and quality of life outcomes
At week 25, treatment with pimicotinib demonstrated an ORR of 54% versus 3.2% for placebo. The study also revealed statistically significant and clinically meaningful improvements across all secondary endpoints related to key patient-reported outcomes in TGCT.
In a press release, Professor Niu Xiaohui, director of the bone and soft tissue tumor diagnosis and research center at Beijing Jishuitan Hospital, said: “The impact that TGCT has on patients goes far beyond the physical presence of the tumor. It affects their ability to work, to move freely, and to engage in everyday activities. In MANEUVER, we observed the highest ORR seen to date with a systemic therapy, together with statistically significant improvements in measures of pain, stiffness, and range of motion. These improvements in outcomes that matter to patients with TGCT and the physicians who care for them show the potential of pimicotinib to allow patients to go about their daily lives with fewer negative effects of their disease.”
Study design and primary endpoints of the MANEUVER trial
The Phase III MANEUVER trial (NCT05804045) is a three-part, randomized, double-blind, placebo-controlled study. It enrolled patients with TGCT who require systemic therapy and have not received prior anti-CSF-1/CSF-1R therapy.
In part one of the study, 94 patients were randomized 2:1 to receive either pimicotinib or placebo for 24 weeks. In addition to the primary endpoint of ORR, key secondary endpoints include tumor volume score, active range of motion, stiffness, pain, and physical function.
Open-label extension and global commercialization plans
Following part one, eligible patients could continue to the open-label study for up to 24 weeks, from which Merck KGaA is expecting results in mid-2025. Finally, patients who complete part two can enter the open-label extension phase for extended treatment and monitoring.
In the press release, Danny Bar-Zohar, appointed CEO healthcare and current global head of R&D and chief medical officer, Merck KGaA, added: “TGCT, although rare, has a significant impact on the daily lives of the primarily working-age adults who live with the disease, due to swelling, pain, stiffness, and limited mobility caused by the growth of these tumors in and around the joints. The landmark global Phase III MANEUVER study data will help redefine how TGCT is treated, and we plan regulatory submissions to start this year.”
Safety profile and licensing agreement with Abbisko Therapeutics
Merck KGaA initially shared results from MANEUVER in November 2024. In addition to the topline results, pimicotinib was well-tolerated, with a safety profile consistent with previously reported data. Treatment-emergent adverse events (TEAEs) leading to discontinuation occurred in 1.6% of patients, while 7.9% experienced TEAEs that led to a dose reduction.2
Pimicotinib is being developed by Abbisko Therapeutics, while Merck KGaA has an exclusive license to commercialize pimicotinib for all indications in the Chinese mainland, Hong Kong, Macau, and Taiwan, plus an option for the rest of world including the US. The companies entered into a commercialization agreement in December 2023.
Phase Ib data of pimicotinib from the time of the agreement showed the inhibitor demonstrated an overall response rate at one-year follow-up of 87.5%, with three complete responses.3
References
1. Pimicotinib Demonstrates Best-in-Class Potential with Significant Efficacy and Clinically Meaningful Improvements in Patients with Tenosynovial Giant Cell Tumor. News release. Merck KGaA. May 28, 2025. Accessed May 28, 2025. https://www.emdgroup.com/en/news/pimicotinib-maneuver-asco-28-05-2025.html
2. Pimicotinib Significantly Improved Outcomes for Patients with Tenosynovial Giant Cell Tumor in a Global Phase III Trial. News release. Merck KGaA. November 12, 2024. Accessed May 28, 2025. https://www.businesswire.com/news/home/20241111864964/en/Pimicotinib-Significantly-Improved-Outcomes-for-Patients-with-Tenosynovial-Giant-Cell-Tumor-in-a-Global-Phase-III-Trial
3. Merck KGaA, Darmstadt, Germany, Strengthens Oncology Portfolio Through Commercialization Agreement With Abbisko for Phase III Asset, Pimicotinib. News release. Merck KGaA. December 4, 2023. Accessed May 28, 2025. https://www.emdgroup.com/en/news/abbisko-pimicotinib-agreement-04-12-2023.html
