Merck announced positive results from the Phase III MANEUVER trial of pimicotinib, an investigational drug developed by Abbisko Therapeutics, for the treatment of tenosynovial giant cell tumor (TGCT). The trial met its primary endpoint, demonstrating a significant improvement in objective response rate (ORR) compared to placebo.
The MANEUVER study, a randomized, double-blind, placebo-controlled trial, enrolled patients with TGCT across China, Europe, the US, and Canada. Participants were administered either 50 mg of pimicotinib once daily or a placebo for 24 weeks. The primary endpoint was the ORR at week 25, assessed using RECIST version 1.1 by blinded independent central review.
Key Findings from the MANEUVER Trial
The study revealed a significant difference in ORR at week 25, with 54.0% of patients in the pimicotinib group achieving an objective response compared to only 3.2% in the placebo group (p<0.0001). This indicates a substantial clinical benefit for patients treated with pimicotinib.
In addition to the primary endpoint, the trial also assessed several secondary endpoints related to patient-reported outcomes. Treatment with pimicotinib resulted in statistically significant and clinically meaningful improvements in stiffness, as measured by the Numeric Rating Scale (NRS; -3.00 mean change from baseline vs. -0.57 for placebo, p<0.0001), and pain, assessed by the Brief Pain Inventory (BPI; -2.32 vs. 0.23 mean change from baseline, p<0.0001).
Safety and Tolerability
Pimicotinib was generally well-tolerated in the MANEUVER trial. The safety profile was consistent with previously reported data, and there was no evidence of cholestatic hepatotoxicity. Treatment-emergent adverse events (TEAEs) leading to treatment discontinuation occurred in only 1.6% (n=1) of patients treated with pimicotinib, while TEAEs leading to dose reduction occurred in 7.9% (n=5) of pimicotinib-treated patients.
Expert Commentary
Professor Niu Xiaohui, Director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital, noted the significant impact of TGCT on young and middle-aged adults, stating, "The swelling, pain, stiffness and limited mobility caused by the disease can have a significant impact on the ability to perform daily activities, limiting patients’ work and social lives." He added that the data from the MANEUVER study, combined with the convenience of once-daily oral administration and pimicotinib’s selective inhibition of CSF-1R, could establish a new treatment paradigm for TGCT.
Pimicotinib's Potential Impact on TGCT Treatment
Pimicotinib, a selective and potent small-molecule inhibitor of colony stimulating factor-1 receptor (CSF-1R), represents a potential new treatment option for TGCT. The disease, characterized by the thickening and overgrowth of joint tissues, significantly impacts patients' lives, causing pain, stiffness, and reduced mobility. Current treatment options, primarily surgery, often face limitations due to high recurrence rates and potential complications.
Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business sector of Merck, emphasized the unmet need for effective and well-tolerated systemic treatments for TGCT. He stated that the Phase III data from MANEUVER confirm earlier Phase I study results, indicating that targeting CSF-1R with pimicotinib offers a promising new approach. Merck and Abbisko are collaborating to review the data and prepare for regulatory submissions in China.
Yaochang Xu, Chairman and CEO of Abbisko Therapeutics, highlighted the global nature of the MANEUVER study, noting that it is the first to enroll both Asian and Western patients with TGCT in balanced proportions. This allows for detailed outcome comparisons and a deeper understanding of disease characteristics across different populations. Xu expressed enthusiasm for collaborating with Merck to pursue registration of pimicotinib as a novel therapy for TGCT in China.
