Journal article
ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma
Journal of Clinical Oncology, Vol.43(6), pp.716-729
02/20/2025
DOI: 10.1200/JCO.24.01034
PMCID: PMC11825507
PMID: 39514826
Abstract
PurposePharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration-approved for adults.MethodsReNeu is an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in 58 adults (≥18 years of age) and 56 children (2 to 17 years of age) with NF1-PN causing significant morbidities. Patients received mirdametinib capsules or tablets for oral suspension (2 mg/m2 twice daily, maximum 4 mg twice daily), regardless of food intake, in 3 weeks on/1 week off 28-day cycles. The primary end point was confirmed objective response rate (ORR; proportion of patients with a ≥20% reduction of target PN volume from baseline on consecutive scans during the 24-cycle treatment phase) assessed by blinded independent central review (BICR) of volumetric magnetic resonance imaging.ResultsTwenty-four of 58 adults (41%) and 29 of 56 children (52%) had a BICR-confirmed objective response during the 24-cycle treatment phase; in addition, two adults and one child had confirmed responses during long-term follow-up. Median (range) target PN volumetric best response was -41% (-90 to 13) in adults and -42% (-91 to 48) in children. Both cohorts reported significant and clinically meaningful improvement in patient- or parent proxy-reported outcome measures of worst tumor pain severity, pain interference, and health-related quality of life (HRQOL) that began early and were sustained during treatment. The most commonly reported treatment-related adverse events were dermatitis acneiform, diarrhea, and nausea in adults and dermatitis acneiform, diarrhea, and paronychia in children.ConclusionIn ReNeu, the largest multicenter NF1-PN trial reported to date, mirdametinib treatment demonstrated significant confirmed ORRs by BICR, deep and durable PN volume reductions, and early, sustained, and clinically meaningful improvement in pain and HRQOL. Mirdametinib was well-tolerated in adults and children.
Details
- Title: Subtitle
- ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma
- Creators
- Christopher L MoertelAngela C HirbeHans H ShuhaiberKevin BielamowiczAlpa Sidhu - University of IowaDavid ViskochilMichael D WeberArmend LokkuL Mary SmithNicholas K ForemanFouad M HajjarRene Y McNall-KnappLauren WeintraubReuben AntonyAndrea T FransonJulia MeadeDavid SchiffTobias WalbertPrakash AmbadyDaniela A BotaCynthia J CampenGurcharanjeet KaurLaura J KlesseStefania MarakaPaul L MootsKathryn NevelMiriam BornhorstAna Aguilar-BonillaSarah ChagnonNagma DalviPunita GuptaZiad KhatibLaura K MetrockP Leia NghiemphuRyan D RobertsNathan J RobisonZsila SadighiStacie StapletonDusica Babovic-VuksanovicTimothy R GershonAhmed RaslanAndrew WalterBrian Van TineCarl KoschmannJamie K CapalJohn SlopisJonathan GillLeia NghiemphuLindsay KilburnMaciej M MrugalaMary Lou SchmidtNick K ForemanRadhika DhamijaRueben AntonyRyan MerrellReNeu Trial Investigators
- Resource Type
- Journal article
- Publication Details
- Journal of Clinical Oncology, Vol.43(6), pp.716-729
- DOI
- 10.1200/JCO.24.01034
- PMID
- 39514826
- PMCID
- PMC11825507
- NLM abbreviation
- J Clin Oncol
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Publisher
- ASCO Publications
- Number of pages
- 716 - 729
- Grant note
- SpringWorks Therapeutics
We thank the patients and families who participated in the trial; the ReNeu site investigators and personnel; the members of the data monitoring committee (Julia Glade-Bender, MD; Ibrahim Qaddoumi, MD, MS; and Barry Turnbull, PhD); Pamela L. Wolters, PhD, of the National Cancer Institute for guidance on PRO measures of pain based on expertise with novel assessment tools; the contributors from SpringWorks Therapeutics (Katie Stabler, BS, and Cindy Garrison, BA, for clinical trial management; Jack Li, PhD, and Samriddhi Chatterjee, MS, for statistical programming and biometrics support; Timothy Bell, MHA, for input on PRO measures; and Abraham Langseth, PhD; Uchenna Iloeje, MD, MPH, FACP; and Wenlin Shao, PhD, for strategic guidance on manuscript development); and Julia Burke, PhD, and Stephen Bublitz, ELS, of MedVal Scientific Information Services, LLC (Princeton, NJ) for medical writing and editorial assistance. The complete list of ReNeu Trial Investigators is provided in Appendix Table A1 (online only).
- Language
- English
- Date published
- 02/20/2025
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984801615602771
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