Pimicotinib Shows Promising Phase 3 Results in Treating Tenosynovial Giant Cell Tumor (TGCT)
Merck, a global leader in science and technology, has released detailed findings from Part 1 of its global Phase 3 MANEUVER trial. The study evaluated the investigational compound pimicotinib, developed by Abbisko Therapeutics for the treatment of tenosynovial giant cell tumor (TGCT). TGCT is a rare and debilitating joint tumor that primarily affects young and middle-aged adults, causing pain, swelling, stiffness, and limited mobility.
Pimicotinib is a potential best-in-class oral inhibitor of the colony stimulating factor-1 receptor (CSF-1R). It works by blocking the CSF-1/CSF-1R signaling pathway, which is believed to drive the proliferation of abnormal cells in TGCT. The MANEUVER trial provides robust evidence supporting pimicotinib’s efficacy and safety in a population with limited non-surgical treatment options.
Primary Endpoint Achieved with Statistically Significant Results
The trial demonstrated that once-daily pimicotinib achieved the primary endpoint, with an objective response rate (ORR) of 54.0% compared to only 3.2% for placebo (p<0.0001). ORR was assessed by a blinded independent review committee (BIRC) using RECIST v1.1 criteria at 25 weeks. This marks the highest ORR reported to date for a systemic therapy targeting TGCT.
“These results reflect not only a significant reduction in tumor size but also improvements in symptoms that impact patients’ quality of life,” said Prof. Niu Xiaohui, Director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital. He noted that TGCT affects more than just joint integrity—it disrupts everyday functions such as working, walking, and basic mobility.
Prof. Niu highlighted that the trial’s findings go beyond clinical measures and underscore pimicotinib’s potential to make meaningful changes in patients’ daily experiences. He described the improvements in pain, stiffness, and range of motion as “unprecedented” in TGCT treatment.
Secondary Endpoints: Consistent Improvement in Patient-Reported Outcomes
Pimicotinib showed statistically significant and clinically meaningful results in all secondary endpoints. These endpoints measured patient-reported outcomes (PROs) central to living with TGCT. Notable improvements were recorded in active range of motion, physical function (PROMIS-PF scale), worst stiffness, and worst pain.
- Active Range of Motion: Improved significantly (p=0.0003)
- Physical Function (PROMIS-PF): Showed statistically significant enhancement (p=0.0074)
- Worst Stiffness: Substantially reduced (p<0.0001)
- Worst Pain: Dramatically improved (p<0.0001)
Interestingly, these improvements were evident even in patients who did not achieve an objective tumor response, indicating pimicotinib’s ability to provide symptomatic relief independent of tumor shrinkage.
Early and Sustained Tumor Response Observed
By week 13 of treatment, 41.3% of patients (26 out of 63) in the pimicotinib group had already achieved an objective response. At the primary data cutoff, 92.1% of pimicotinib-treated patients (58 out of 63) showed tumor shrinkage. Notably, one patient achieved a complete response while 33 reached partial responses. The median duration of response had not been reached, suggesting long-term efficacy.
The study also used the Tumor Volume Score (TVS), a metric tailored for TGCT evaluation. The results were compelling—61.9% of pimicotinib-treated patients experienced a reduction in tumor volume of at least 50%, compared to only 3.2% of those on placebo (p<0.0001).
Global Scope and Clinical Significance
The MANEUVER study enrolled participants from China, Europe, and North America, making the results globally relevant. TGCT is a rare disease that disproportionately affects adults in their prime working years. As such, improvements in joint function and symptom control have the potential to significantly enhance work productivity and overall life quality.
Danny Bar-Zohar, CEO Healthcare and Global Head of R&D and Chief Medical Officer at Merck, stated, “TGCT, although rare, has a disproportionate impact on working-age adults. The MANEUVER study’s findings may redefine how we treat this disease. Based on these promising results, we are initiating regulatory submissions this year.”
Safety Profile and Tolerability
Pimicotinib demonstrated a favorable safety profile with no new safety signals identified. The drug was well-tolerated, with a low incidence of adverse events leading to treatment discontinuation (1.6%). Adverse events leading to dose reduction occurred in only 7.9% of patients.
Importantly, there was no evidence of cholestatic hepatotoxicity—a concern with some CSF-1R inhibitors. Nor were there reports of hair or skin hypopigmentation, which have been associated with other compounds in this class. This suggests that pimicotinib may offer a safer long-term treatment option.
Regulatory Pathway and Potential Impact
Merck and Abbisko Therapeutics plan to move forward swiftly with regulatory submissions, based on the compelling data from MANEUVER. The presentation of these findings at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting underscores the potential importance of pimicotinib in reshaping the TGCT treatment paradigm.
TGCT, once considered primarily a surgical disease, has increasingly been acknowledged as requiring systemic solutions—particularly in diffuse or inoperable cases. Pimicotinib could fulfill this unmet need by offering an effective oral therapy that is both convenient and well-tolerated.
The combination of high objective response rates, robust symptom control, early onset of action, and manageable side effects suggests pimicotinib could become the new standard of care for patients with TGCT who are not candidates for surgery or whose disease recurs.
