289P Manageable longer-term safety with the highly-selective colony stimulating factor-1 receptor (CSF-1R) inhibitor pimicotinib in patients with tenosynovial giant cell tumor (TGCT) in the global MANEUVER trial

Background: Mirdametinib is the first MEK1/2 inhibitor approved by the US Food and Drug Administration for both adults and children (2 years) with NF1 who have symptomatic PN not amenable to complete resection and by the European Commission for both adults and children (2 years) with NF1 who have symptomatic, inoperable PN. Methods:In ReNeu (NCT03962543), mirdametinib (capsule or tablets for oral suspension) was administered in 3-weeks-on/1-week-off 28-day cycles for the 24-cycle (1-cycle=28-days) treatment phase.Patients could continue mirdametinib in an optional LTFU.We report results through 12 June 2024, 9 months after the primary analysis.Results: Fifty-eight adults and 56 children received mirdametinib.Median (range) duration of treatment was 21.8 (0.4, 54.4) months in adults and 25.4 (1.6, 48.5) months in children.Among LTFU-eligible patients, 26/31 (84%) adults and 32/37 (86%) children entered LTFU.Confirmed objective response rate (ORR; treatment plus LTFU phases) was 47% (27/58; 95% CI, 33%, 60%) in adults and 55% (31/56; 95% CI, 42%, 69%) in children.Among confirmed responders, 18 adults and 19 children achieved a deep response (best target PN volume reduction from baseline of >50%).Median (range) best percentage change from baseline in target PN volume was -41% (-90%, 13%) in adults and -43% (-98%, 48%) in children.Median duration of response was not reached for either age cohort.Treatment-related adverse events (TRAEs) in 25% of patients were dermatitis acneiform, diarrhea, nausea, and vomiting in adults; and diarrhea, dermatitis acneiform, and paronychia in children.Grade 3 TRAEs occurred in 17% of adults and 25% of children.Dose interruptions, dose reductions, and discontinuations due to TRAEs occurred in 9%, 17%, and 22%, respectively, of adults, and 14%, 14%, and 9%, respectively, of children. Conclusions:Longer duration of mirdametinib demonstrated improved confirmed ORR, additional deep responses in adults and children, and continued to be well tolerated with no new safety signals in patients with NF1-PN.