Targeted treatment for aggressive tenosynovial giant cell tumor

The global 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), a tumor type of mesenchymal origin which is considered ultra-rare with an incidence of less than one case per million inhabitants per year.

Previously presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, findings from this study—co-authored by César Serrano, a Medical Oncologist at the Vall d’Hebron University Hospital and Head of VHIO’s Sarcoma Translational Research Group —published today in The Lancet^*.

“Tenosynovial giant cell tumor is a rare, locally aggressive mesenchymal tumor. Affecting otherwise healthy adults, particularly young people, it is 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.

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, and the observed tumor volume reduction rate was 63.5% versus 3.3%, respectively.

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. Thpese data support the efficacy of this targeted therapy in improving symptoms and quality of life.

“With an overall response rate of over 50% in a diverse patient population from around the world, results of this pivotal study show significant improvements in symptoms and quality of life, representing an effective and well-tolerated treatment option,” concluded Serrano.

Pimicotinib is approved as systemic treatment for TGCT patients who are not amenable to surgery in China, and was previously granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA), as well as 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.

Reference: *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. Pimicotinib in TGCT: results of the global randomised placebo-controlled phase 3 MANEUVER study. The Lancet, Published Online March 5, 2026 https://doi.org/10.1016/S0140-6736(25)02602-9