Updated data of efficacy and safety of luvometinib (FCN-159) in pediatric participants with neurofibromatosis type 1 from a multi-center, open-label, single-arm phase 2 study.

10044 Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease characterized by multiple progressive tumor and non-tumor manifestations, with abnormal activating MAPK pathway. Plexiform neurofibromas (PN) presents in 20-50% of NF1 patients (pts) and may cause serious complications. One MEK1/2 inhibitor was approved for pediatric pts with NF1-related PN in US, EU and China, but therapeutic options remain limited. Luvometinib is a highly potent selective anti-tumorigenic inhibitor of MEK1/2, potentially effective in NF1-related PN. Previous studies have confirmed that luvometinib is expected to be a targeted therapy for neurofibromatosis type 1 in pediatric patients (pts). Methods: This multi-center, open-label phase 2 clinical trial is to assess safety and efficacy of luvometinib in pediatric pts with NF1- related PN. The primary endpoint was objective response rate (ORR) evaluated by investigators (INV). The key secondary endpoint was ORR evaluated by Blinded independent review committee (BIRC), and other secondary endpoints include 1-year PFS and others. Preliminary findings from the phase 2 trial were previously disclosed at ASCO 2024. Here, we present the updated efficacy and safety results in pediatric participants. Results: As of data cut-off (September 23, 2024), 46 pediatric pts were enrolled and treated with a dose of 5 mg/m 2 (the recommended phase 2 dose according to phase 1 study). The median follow-up time was 25.1 months. ORR evaluated by INV was 60.5% (95%CI: 44.4, 75.0), and 26 pts had partial response. ORR evaluated by BIRC was 44.2% (95%CI: 29.1, 60.1), and 19 pts had partial response. 11 of 14 pts (78.6%) with tumor pain at baseline (overall tumor pain NRS≥2) decreased to 0 points. The median DOR and median PFS were still not reached. 1-year PFS rate evaluated by INV was 95.3%. 45 pts (97.8%) experienced treatment-related adverse events (TRAEs). Among these, grade ≥3 TRAEs occurred in 10 pts (21.7%), including folliculitis(4.3%), dermatitis acneiform (4.3%), blood creatine phosphokinase increased (4.3%), ejection fraction decreased (2.2%), upper respiratory tract infection (2.2%), pneumonia (2.2%), anemia (2.2%) and gastrointestinal disorders (2.2%). 2 pts (3.1%) reported treatment-related serious adverse events. 14 pts (30.4%) experienced TRAEs led dose interruption. No reported TEAE led to dose reduction, discontinuation or death. No new safety signal was observed. Conclusions: Overall, luvometinib was well-tolerated and demonstrated promising anti-tumor activity in pediatric participants with NF1-related PN. Long-term efficacy and safety follow-up are ongoing. Clinical trial information: NCT04954001 .