The pivotal phase 3 MANEUVER trial is a three-part, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of pimicotinib, an oral, highly selective and potent small molecule CSF-1 receptor inhibitor, in patients with tenosynovial giant cell tumor (TGCT) who are eligible for systemic therapy and have not received prior anti-CSF-1/CSF-1R therapy.
The findings from the double-blind part 1 of this study, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting* by co-Principal Investigator Hans Gelderblom, Head of the Medical Oncology Department at the Leiden University Medical Center (LUMC), Netherlands, represent an important step forward in changing the treatment landscape for patients with TGCT.
“Tenosynovial giant cell tumor is a rare, locally aggressive mesenchymal tumor caused by the overexpression of the CSF-1 protein, which occurs in up to 95 per cent of all cases. This often-recurring soft tissue tumor is associated with high morbidity due to swelling, pain, stiffness, and limited mobility of the affected joints, and significantly impacts quality of life of these patients who currently have very limited treatment options,” said César Serrano, a Medical Oncologist of the Vall d’Hebron University Hospital, Head of VHIO’s Sarcoma Translational Research Group, and a co-author of this study.
MANEUVER, the first global phase 3 trial to recruit patents from Asia, EU and North America who were candidates for systemic therapy, enrolled 94 patients who were randomly assigned to receive pimicotinib or placebo (63 versus 31 patients). At week 25, the objective response rate was significantly higher in patients who received pimicotinib, 54% compared to 3.2% in patients assigned to placebo.
The reduction in tumor burden in patients treated with pimicotinib led to statistically significant improvements in parameters related to joint function such as range of motion, stiffness, pain control, and general physical function. These promising results support the potential use of pimicotinib as systemic therapy for patients with TGCT.
“With an overall response rate of over 50% in a diverse patient population from around the world, results from part 1 of this pivotal study show significant improvements in symptoms and quality of life, representing an effective and well-tolerated treatment option,” concluded Serrano.
Pimicotinib was previously granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) and China’s National Medical Products Administration (NMPA) for the treatment of TGCT patients who are not amenable to surgery, and priority medicine designation by the European Medicines Agency (EMA). It was also granted orphan drug designation by EMA in January 2024 for the treatment of inoperable TGCT.
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Reference
*2025 ASCO Annual Meeting, May 30 – June 3, Chicago, IL
Corresponding session details:
Oral Abstract Session: Sarcoma
Date: June 1, 2025
Time: 09:45h CT, 16:45h CEST
Room: S100a
Chairs: Alberto S. Pappo, MD, Department of Oncology, St. Jude Children’s Research Hospital, and Elise F Nassif Haddad, MD, PhD, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center.
Speaker: Hans Gelderblom.
- Pimicotinib in tenosynovial giant cell tumor (TGCT): Efficacy, safety and patient-reported outcomes of phase 3 MANEUVER study. Xiaohui Niu, Vinod Ravi, Javier Martin Broto, Yong Zhou, Albiruni R. Abdul Razak, Ramy Saleh, Jingnan Shen, Tang Liu, Silvia Stacchiotti, Kamalesh K. Sankhala, César Serrano, Jing Wang, Yingqi Hua, Piotr Rutkowski, Xiaojing Zhang, Yi Feng, Tao Li, Giacomo G. Baldi, Hairong Xu, Hans Gelderblom.
