Abbisko Therapeutics has announced positive topline results from its Phase 3 MANEUVER study, evaluating pimicotinib for the treatment of tenosynovial giant cell tumor (TGCT). The study met its primary endpoint, demonstrating a statistically significant improvement in objective response rate (ORR) at Week 25 compared to placebo.
The MANEUVER study, a randomized, double-blind, placebo-controlled trial, enrolled patients with TGCT eligible for systemic therapy who had not previously received anti-CSF1/CSF1R therapy. Patients were randomized 2:1 to receive either 50 mg QD of pimicotinib (n=63) or placebo (n=31) for 24 weeks. The primary endpoint was ORR at Week 25 as measured by RECIST v1.1 per Blinded Independent Review Committee (BIRC) in the intent-to-treat (ITT) population.
Significant Efficacy Demonstrated
The study revealed that pimicotinib achieved an ORR of 54.0% at Week 25, compared to 3.2% for placebo (p<0.0001). Treatment with pimicotinib also resulted in statistically significant and clinically meaningful improvements in secondary endpoints, including stiffness (NRS; -3.00 mean change from baseline vs. -0.57 for placebo, p<0.0001) and pain (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, commented on the potential impact of the findings: "Based on these new data from the MANEUVER study, together with once-daily oral administration that may promote long-term adherence and pimicotinib's selective inhibition of CSF-1R, this investigational medicine has the potential to establish a new treatment paradigm for patients with TGCT."
Safety and Tolerability
Pimicotinib was well-tolerated in the MANEUVER study, with a safety profile consistent with prior reported data. Notably, there was no evidence of cholestatic hepatotoxicity. Treatment-emergent adverse events (TEAEs) leading to treatment discontinuation occurred in 1.6% of patients treated with pimicotinib, while TEAEs leading to dose reduction occurred in 7.9% of pimicotinib-treated patients.
Phase 1 Data Update
Abbisko also announced updated results from its Phase 1 open-label study, which evaluated the safety and efficacy of pimicotinib in TGCT patients. As of June 30, 2024, data from 42 patients who received the 50 mg dose of pimicotinib showed a best ORR of 85.0% by RECIST v1.1 per IRC. The median duration of response was not reached, and 69.0% of patients remained on treatment. Continuous and gradual improvements in tumor regression, pain and stiffness relief, and joint mobility were observed during long-term treatment.
Collaboration with Merck
In December 2023, Abbisko Therapeutics entered into a licensing agreement granting Merck exclusive rights to commercialize pimicotinib in Chinese mainland, Hong Kong, Macau, and Taiwan, with an exclusive option for global commercial rights.
Danny Bar-Zohar, global head of research & development and chief medical officer for the healthcare business sector of Merck, stated, "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. As we work with Abbisko to review the data from this study and prepare to share it with regulators in China, we are focused on our shared goal of bringing pimicotinib to patients in need."
