EMD Serono announced positive results from the global Phase 3 MANEUVER trial of pimicotinib, an investigational colony stimulating factor-1 receptor (CSF-1R) inhibitor, in patients with tenosynovial giant cell tumor (TGCT). The once-daily oral therapy achieved a statistically significant 54.0% objective response rate compared to 3.2% for placebo at week 25 (p<0.0001), meeting the study's primary endpoint.
Comprehensive Efficacy Across Multiple Endpoints
The MANEUVER study demonstrated statistically significant improvements across all five key secondary endpoints. Pimicotinib showed clinically meaningful benefits in active range of motion (p=0.0003) and physical function measured by PROMIS-PF scale (p=0.0074). The treatment also significantly reduced worst stiffness (p<0.0001) and worst pain (p<0.0001).
Analysis of tumor volume score, an endpoint specifically designed for TGCT, revealed that 61.9% of patients treated with pimicotinib experienced at least 50% reduction in tumor volume compared to 3.2% for placebo (p<0.0001). Nearly all patients in the pimicotinib group (58 of 63 patients; 92.1%) showed decreased tumor size based on RECIST v1.1 criteria, with one patient achieving complete response and 33 patients achieving partial response.
Rapid Onset and Sustained Response
The therapeutic effect of pimicotinib demonstrated early onset, with 41.3% (26 of 63) of patients experiencing objective response after just 13 weeks of treatment. The median duration of response had not been reached by the data cutoff for primary analysis, suggesting sustained therapeutic benefit.
"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," said Prof. Niu Xiaohui, Director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital. "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."
Favorable Safety Profile
Pimicotinib demonstrated a well-tolerated safety profile consistent with previously reported data. Treatment-emergent adverse events leading to discontinuation occurred in only one patient (1.6%) in the pimicotinib group, while dose reductions were required in 7.9% (n=5) of treated patients. Notably, the safety analysis showed no evidence of cholestatic hepatotoxicity or hair/skin hypopigmentation.
Study Design and Patient Population
The pivotal Phase 3 MANEUVER study enrolled 94 patients across China (n=45), Europe (n=28), and North America (n=21). Participants were randomized 2:1 to receive either 50 mg once-daily pimicotinib (n=63) or placebo (n=31) for 24 weeks in the double-blind Part 1 phase. The study included patients with TGCT requiring systemic therapy who had not received prior anti-CSF-1/CSF-1R therapy.
Regulatory Pathway and Clinical Impact
Pimicotinib has received breakthrough therapy designation from both the China National Medical Products Administration (NMPA) and the US Food and Drug Administration (FDA) for unresectable TGCT, as well as priority medicine (PRIME) designation from the European Medicines Agency (EMA). The drug was recently granted Priority Review by China's Center for Drug Evaluation.
"The landmark global Phase 3 MANEUVER study data will help redefine how TGCT is treated, and we plan regulatory submissions to start this year," said Danny Bar-Zohar, appointed CEO Healthcare and current Global Head of R&D and Chief Medical Officer at EMD Serono.
The findings will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting on June 1 (Abstract #11500). Eligible patients from Part 1 can continue to the open-label Part 2 for up to 24 additional weeks, with results expected in mid-2025.
