(P 543) MANEUVER STUDY: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF PIMICOTINIB (ABSK021) TO ASSESS THE EFFICACY AND SAFETY IN PATIENTS WITH TENOSYNOVIAL GIANT CELL TUMOR

Objective: TGCT is a rare type of locally aggressive neoplasm that is primarily caused by overexpression of colony-stimulating factor 1 (CSF1) gene. Pimicotinib is an oral, highly potent, and selective small-molecule antagonist of CSF-1R with minimum inhibition of c-Kit and PDGFR. In a Phase 1b study, Pimicotinib demonstrated significant antitumor activity with the ORR of 77.4% in 50 mg QD cohort by IRC based on RECIST1.1, and a favorable safety profile with no apparent hepatotoxicity (Xu et al, ASCO 2023) in TGCT patients. No apparent ethnic differences were observed for PK and PD data among different ethnic groups based on data from Phase 1 study. Pimicotinib has been granted Breakthrough Therapy Designation (BTD) by China NMPA and US FDA, and PRIority MEdicines (PRIME) Designation by the European Medicines Agency for treating TGCT. MANEUVER study (NCT05804045) is a Phase 3, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of Pimicotinib at the dose of 50 mg QD in patients with unresectable TGCT. The study marks the first global Phase 3 trial assessing a CSF-1R inhibitor in TGCT patients across Asia, North America and Europe.

Methods: MANEUVER study consists of two parts. Part 1 is a double-blind phase, approximately 90 eligible patients will be randomized in a 2:1 ratio to 50mg QD ABSK021 treatment group or matching placebo group and will receive consecutive treatment until the completion of Part 1. The randomization will be stratified by geographical location, China vs. non-China sites. All patients who complete Part 1 and meet eligibility criteria will proceed to Part 2. In Part 2, open-label treatment phase, all patients entering this phase will receive open-label 50 mg QD of ABSK021 until the completion of 24 weeks of dosing or withdrawal from the study. Patients who complete 24 weeks of dosing in Part 2 may be eligible for extended treatment.

The primary endpoint is 25-week ORR by Blinded Independent Review Committee (BIRC) based on RECIST 1.1. Key secondary endpoints comprise 25-week ORR by BIRC based on Tumor Volume Score, the mean change from baseline in Range of Motion of the affected joint at week 25, the mean change from baseline in the Worst Stiffness and Worst Pain NRS score at week 25, and the mean change from baseline in the PROMIS Physical Functioning score at week 25. Key inclusion criteria include patients that are, histologically confirmed TGCT and not amenable to surgical resection, existing measurable disease, willingness and ability to complete PRO assessments, symptomatic disease (based on level of pain and stiffness), and age of 18 or older. Key exclusion criteria include previous treatment with highly selective inhibitors targeting CSF-1/CSF-1R (Imatinib and Nilotinib are allowed), known metastatic TGCT or MRI contraindications, major surgery or previous anti-tumor therapy within 4 weeks prior to randomization. An independent Data Monitoring Committee will be established to continuously monitor the safety profile and oversee the overall conduct of the study.

Results: Enrollment is ongoing, approximately 40 sites around the world will participate in this study.

Conclusion: Not applicable