Pimicotinib Demonstrates Significant Efficacy in Phase 3 Trial for Tenosynovial Giant Cell Tumor
Key Insights
Pimicotinib (ABSK021) significantly improved the objective response rate (ORR) in patients with tenosynovial giant cell tumor (search) (TGCT (search)) compared to placebo in the phase 3 MANEUVER trial.
The ORR at week 25 was 54.0% for pimicotinib versus 3.2% for placebo (P < .0001), meeting the primary endpoint of the study.
Secondary endpoints, including stiffness and pain reduction, also showed statistically significant and clinically meaningful improvements with pimicotinib treatment.
Pimicotinib (ABSK021) has shown a significant improvement in objective response rate (ORR) compared to placebo in patients with tenosynovial giant cell tumor (search) (TGCT (search)), according to results from the phase 3 MANEUVER trial (NCT05804045). The study's findings indicate a potential new treatment paradigm for this rare tumor affecting young and middle-aged adults.
The MANEUVER trial's primary endpoint was met with an ORR of 54.0% in the pimicotinib arm compared to just 3.2% in the placebo arm at week 25 (P < .0001). Secondary endpoints also demonstrated significant improvements. The mean change in stiffness, measured by the Numeric Rating Scale (NRS), was -3.00 from baseline in the pimicotinib group versus -0.57 in the placebo group (P < .0001). Similarly, the mean change in pain, assessed by the Brief Pain Inventory (BPI), was -2.32 versus 0.23 in the pimicotinib and placebo arms, respectively (P < .0001).
Impact on TGCT Patients
TGCT (search) primarily affects young and middle-aged adults, causing swelling, pain, stiffness, and limited mobility in the joints. According to Niu Xiaohui, MD, director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital, these symptoms can significantly impact patients' ability to perform daily activities, affecting their work and social lives. Current treatment often involves surgery, but high recurrence rates and potential complications from repeated surgical interventions pose challenges for patients, creating a need for effective systemic therapies.
Study Design and Key Findings
The MANEUVER trial was a three-part, randomized, double-blind, placebo-controlled study. It enrolled patients aged 18 years and older with histologically confirmed unresectable TGCT (search). Key inclusion criteria included measurable disease per RECIST 1.1 criteria (at least one lesion of ≥2 cm), an ECOG performance status of 0 or 1, and adequate organ and bone marrow function. Patients were randomized 2:1 to receive 50 mg of pimicotinib once daily (n = 63) or placebo (n = 31) for 24 weeks in the double-blind part 1. Eligible patients could continue treatment in an open-label extension for up to 24 additional weeks in part 2, with a further open-label extension and safety follow-up in part 3.
Pimicotinib was generally well-tolerated, with a safety profile consistent with previous data. Treatment-emergent adverse effects led to treatment discontinuation and dose reduction in 1.6% and 7.9% of patients in the pimicotinib arm, respectively. Notably, no instances of cholestatic hepatotoxicity were reported.
Potential for a New Treatment Paradigm
"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 (search), this investigational medicine has the potential to establish a new treatment paradigm for patients with TGCT (search)," Dr. Xiaohui stated in a news release.