EMD Serono announced longer-term results from the global Phase 3 MANEUVER trial showing that pimicotinib, an investigational CSF-1R inhibitor, demonstrated deepening and durable tumor responses in patients with tenosynovial giant cell tumor (TGCT). With a median follow-up of 14.3 months, the objective response rate increased considerably to 76.2% (95% CI: 63.8, 86.0) by blinded independent review committee per RECIST v1.1, up from 54% at Week 25.
Enhanced Efficacy Over Time
The latest analysis included 63 patients who received pimicotinib for 24 weeks in Part 1 and continued treatment in the open-label phase. Beyond the primary RECIST v1.1 endpoint, the objective response rate based on tumor volume score (TVS), an endpoint designed specifically for TGCT, increased to 74.6% (95% CI: 62.1, 84.7) from 61.9% at Week 25.
At the time of data cutoff, the median duration of response was not reached (range: 0.03-19.81 months), with 93.7% of pimicotinib-treated patients experiencing tumor size reduction at longer-term follow-up. Patients initially randomized to placebo who switched to pimicotinib in the open-label phase (n=31) achieved an ORR of 64.5% with a median follow-up of 8.5 months after switching.
Sustained Functional Improvements
Pimicotinib demonstrated clinically meaningful improvements in patient-reported outcomes through week 73. For relative range of motion, the treatment showed a mean change from baseline of 23.9%, increased from 15.6% at week 25. The drug continued to show improvements in physical function as measured by the PROMIS-PF scale, along with reductions in stiffness measured by the Worst Stiffness Numeric Scale Rating and pain reduction via Brief Pain Inventory worst pain rating.
"These tumor responses not only persist but deepen over time," said Prof. Niu Xiaohui, Director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital. "Importantly, we also see continued improvements beyond one year in the patient-reported symptoms and functional outcomes that truly make a difference in patients' abilities to go about their daily lives."
Safety Profile Maintained
At longer-term follow-up, patients who received pimicotinib throughout the study showed no new safety signals and no evidence of cholestatic hepatotoxicity, drug-induced liver injury, or hair/skin hypopigmentation. Most treatment-emergent adverse events remained mild in severity and were manageable.
Regulatory Progress
An application for marketing authorization of pimicotinib as a Class 1 innovative drug for adult patients with TGCT has been accepted for review by the Center for Drug Evaluation of the China National Medical Products Administration (NMPA). Additional applications are planned in the U.S. and other markets worldwide.
Study Design and Patient Impact
The MANEUVER study is a three-part, randomized, double-blind, placebo-controlled trial conducted across China (n=45), Europe (n=28), and the U.S. and Canada (n=21). In Part 1, 94 patients were randomized 2:1 to receive either 50 mg once daily of pimicotinib (n=63) or placebo (n=31) for 24 weeks.
Pimicotinib has received breakthrough therapy designation from both the NMPA and FDA, plus priority medicine designation from the European Medicines Agency. The drug is a novel, orally administered, highly selective and potent small-molecule inhibitor of CSF-1R, with Merck KGaA holding worldwide commercialization rights.
"TGCT causes pain, stiffness, and loss of range of motion, affecting patients' ability to participate in activities of daily living," said Sydney Stern, PhD, MS, from TGCT Support. "Addressing their symptoms enables patients to be the parents, partners, carers, and people they want to be without wondering when their TGCT will take over their life again."
