Ctni-06. Update From the Long-term Follow-up (ltfu) Phase of Reneu: a Pivotal Phase 2b Trial of Mirdametinib in Children and Adults With Neurofibromatosis Type 1 (nf1)-associated Symptomatic Plexiform Neurofibroma (pn)
Year: 2025
Type: conference-abstract
Abstract: BACKGROUND Mirdametinib is the first FDA-approved MEK1/2 inhibitor for both adults and children ≥2 years with NF1 who have symptomatic PN not amenable to complete resection. We report results from the phase 2b ReNeu trial (NCT03962543), including the LTFU. METHODS In ReNeu, mirdametinib was administered in 3-weeks-on/1-week-off 28-day cycles. Following the 24-cycle treatment phase, patients could continue mirdametinib in an optional LTFU. We report results through June 12, 2024, approximately 9 months from the previous data cutoff. 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+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 (DoR) 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 Improved confirmed ORR was observed with longer duration of mirdametinib, with additional deep responses achieved in both adults and children. Mirdametinib continued to be well tolerated with a manageable safety profile and no new safety signals in the LTFU.
Source: Neuro-Oncology
Authors: Angela Hirbe, Christopher Moertel, Hans Shuhaiber, David Viskochil, Alpa Sidhu, Julia Meade, Lauren Weintraub, Abraham Langseth, Michael Weber, Armend Lokku, Fouad Hajjar, Reuben Antony, David Schiff, Ahmed Raslan, Kathryn Nevel, Dusica Babovic-Vuksanovic, Timothy Gershon
Institutions: Washington University in St. Louis, University of Minnesota, University of Florida Health, University of Florida, University of Utah, University of Iowa Health Care, University of Pittsburgh, Albany Medical Center Hospital, SpringWorks Therapeutics (United States), AdventHealth for Children, University of California, Davis, University of Virginia Medical Center, Oregon Health & Science University, Indiana University Health, Indiana University Hospital, Indiana University School of Medicine, Mayo Clinic, Emory University
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416140580
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