TY - JOUR
T1 - ReNeu
T2 - A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma
AU - Moertel, Christopher L.
AU - Hirbe, Angela C.
AU - Shuhaiber, Hans H.
AU - Bielamowicz, Kevin
AU - Sidhu, Alpa
AU - Viskochil, David
AU - Weber, Michael D.
AU - Lokku, Armend
AU - Smith, L. Mary
AU - Foreman, Nicholas K.
AU - Hajjar, Fouad M.
AU - McNall-Knapp, Rene Y.
AU - Weintraub, Lauren
AU - Antony, Reuben
AU - Franson, Andrea T.
AU - Meade, Julia
AU - Schiff, David
AU - Walbert, Tobias
AU - Ambady, Prakash
AU - Bota, Daniela A.
AU - Campen, Cynthia J.
AU - Kaur, Gurcharanjeet
AU - Klesse, Laura J.
AU - Maraka, Stefania
AU - Moots, Paul L.
AU - Nevel, Kathryn
AU - Bornhorst, Miriam
AU - Aguilar-Bonilla, Ana
AU - Chagnon, Sarah
AU - Dalvi, Nagma
AU - Gupta, Punita
AU - Khatib, Ziad
AU - Metrock, Laura K.
AU - Nghiemphu, P. Leia
AU - Roberts, Ryan D.
AU - Robison, Nathan J.
AU - Sadighi, Zsila
AU - Stapleton, Stacie
AU - Babovic-Vuksanovic, Dusica
AU - Gershon, Timothy R.
N1 - Publisher Copyright:
© 2024 American Society of Clinical Oncology
PY - 2025/2/20
Y1 - 2025/2/20
N2 - PURPOSE – Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration–approved for adults.METHODS – ReNeu 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.RESULTS – Twenty-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.CONCLUSION – In 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.
AB - PURPOSE – Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration–approved for adults.METHODS – ReNeu 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.RESULTS – Twenty-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.CONCLUSION – In 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.
UR - https://www.scopus.com/pages/publications/85209706506
UR - https://www.scopus.com/pages/publications/85209706506#tab=citedBy
U2 - 10.1200/JCO.24.01034
DO - 10.1200/JCO.24.01034
M3 - Article
C2 - 39514826
AN - SCOPUS:85209706506
SN - 0732-183X
VL - 43
SP - 716
EP - 729
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 6
ER -