Pimicotinib, an investigational oral small molecule inhibitor of colony stimulating factor-1 receptor (CSF-1R), has demonstrated significant improvements in patient outcomes in the Phase III MANEUVER study for tenosynovial giant cell tumor (TGCT). The study, a randomized, double-blind, placebo-controlled trial, assessed the efficacy and safety of pimicotinib in patients with TGCT eligible for systemic therapy who had not received prior anti-CSF-1/CSF-1R therapy.
The MANEUVER study included 94 patients randomized 2:1 to receive either 50 mg QD of pimicotinib (n=63) or placebo (n=31) for 24 weeks. The primary endpoint was objective response rate (ORR) at week 25, as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review in the intent-to-treat (ITT) population.
Clinically Meaningful Improvements
The study also demonstrated statistically significant and clinically meaningful improvements in secondary endpoints, including stiffness (Numeric Rating Scale [NRS]: -3.00 mean change from baseline vs. -0.57 for placebo, p<0.0001) and pain (Brief Pain Inventory [BPI]: -2.32 vs. 0.23 mean change from baseline, p<0.0001).
Professor Niu Xiaohui, Director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital, noted, "TGCT tends to be a disease of the young... Treatment often involves surgery, yet the high recurrence rate and potential complications from repeated surgical interventions can be very challenging for patients to deal with, creating an urgent need for systemic therapy that could control tumor growth."
Safety and Tolerability
Pimicotinib was well-tolerated in the MANEUVER study, with a safety profile consistent with previously reported data. Treatment-emergent adverse events (TEAEs) leading to treatment discontinuation occurred in 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. There was no evidence of cholestatic hepatotoxicity.
Global Collaboration
Abbisko Therapeutics and Merck KGaA, Darmstadt, Germany, are collaborating to bring pimicotinib to patients in need. Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business sector of Merck KGaA, stated, "There is a tremendous unmet need for effective, well-tolerated systemic treatment for TGCT... These Phase III data from MANEUVER confirm results of Abbisko’s Phase I study, indicating that targeting CSF-1R with pimicotinib has the potential to offer a new treatment option for patients."
Yaochang Xu, Chairman and CEO of Abbisko Therapeutics, emphasized the global nature of the study: "As the first global trial to enroll both Asian and Western patients with TGCT in balanced proportions across multiple regions, MANEUVER is a landmark global study that allows for detailed outcome comparisons."
About TGCT
Tenosynovial giant cell tumor (TGCT) is a rare, benign, and locally aggressive disease originating in the synovial lining of joints, bursae, and tendon sheaths. It leads to thickening and overgrowth of these tissues, causing joint pain, stiffness, swelling, and reduced range of motion. Current treatment primarily involves surgery, but recurrence rates are high, highlighting the need for effective systemic therapies.
