ABBISKO-B(02256): The key phase 3 study of imatinib in treating TGCT patients achieved positive top-line results, as well as the latest phase 1 study results of imatinib in treating TGCT.

ABBISKO-B (02256) announced on November 12, 2024, that Shanghai Heyu Biomedical Technology Co., Ltd. (Heyu Medicine) has achieved positive top-line results in the MANEUVER pivotal Phase 3 study of the small molecule CSF-1R inhibitor pexidartinib for the treatment of tenosynovial giant cell tumor (TGCT) patients, as well as the latest Phase 1 study results of pexidartinib in treating TGCT. The MANEUVER study met its primary endpoint, with the objective response rate (ORR) of pexidartinib at Week 25 being 54.0%, compared to 3.2% in the placebo group (p<0.0001). Compared to the placebo group, the study also showed significant improvements in all key secondary endpoints evaluated at Week 25, including ORR based on tumor volume score, active joint motion, stiffness, pain severity, and physical function. The once-daily oral pexidartinib treatment demonstrated good tolerability, with a very low proportion of treatment discontinuation due to treatment-related adverse events. The latest Phase 1b study results of pexidartinib showed an optimal ORR of 85.0% and a median treatment duration of 20 months. The MANEUVER study is a randomized, double-blind, placebo-controlled pivotal Phase 3 clinical trial consisting of three parts aimed at evaluating the efficacy and safety of pexidartinib in TGCT patients who meet the conditions for systemic treatment and have not received prior anti-CSF1/CSF1R therapy. The study is being conducted in China (45 patients), Europe (28 patients), the United States, and Canada (21 patients). In the first part of the double-blind study stage, 94 patients were randomized in a 2:1 ratio to receive 50 mg QD of pexidartinib (n=63) or placebo (n=31) for 24 weeks. The primary endpoint was the ORR at Week 25 in the intention-to-treat (ITT) population as assessed by an independent review committee using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints included tumor volume-based scoring, active joint motion, stiffness measured by a Numeric Rating Scale (NRS), pain severity measured by Brief Pain Inventory (BPI), and physical function assessment measured by PROMIS. Detailed efficacy and safety data from the first part of the MANEUVER study will be presented at an upcoming medical conference. After the completion of the first part of the double-blind study, eligible patients can continue to the open-label second part for up to 24 weeks of treatment. Patients who complete the second part of the study can enter an open-label extension period (Part 3) for extended treatment and safety follow-up. The study met its primary endpoint in the ITT population, showing a statistically and clinically significant improvement in ORR at Week 25 compared to placebo. In the ITT population, the ORR at Week 25 for the pexidartinib group was 54.0% compared to 3.2% in the placebo group (p<0.0001). In the MANEUVER study, pexidartinib demonstrated good tolerability, with safety data consistent with previously reported data, and no observed cases of cholestatic liver toxicity. The proportion of patients in the pexidartinib group who had treatment discontinuation or dose reduction due to treatment-emergent adverse events (TEAE) during treatment was 1.6% (1 case) and 7.9% (5 cases), respectively. Heyu Medicine also announced the latest results of the Phase 1 open-label multicenter study evaluating the safety and efficacy of pexidartinib in TGCT patients. The poster titled "Long-term efficacy and safety profile of pexidartinib (ABSK021) in tenosynovial giant cell tumors (TGCT): update from the Phase 1b study" will be presented at the Connective Tissue Oncology Society (CTOS) annual meeting in San Diego, USA, from November 13 to November 16, 2024.