ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma
Authors: Moertel Christopher L. , Hirbe Angela C. , Shuhaiber Hans H. , Bielamowicz Kevin , Sidhu Alpa , Viskochil David , Weber Michael D. , Lokku Armend , Smith L. Mary , Foreman Nicholas K. , Hajjar Fouad M. , McNall-Knapp Rene Y. , Weintraub Lauren , Antony Reuben , Franson Andrea T. , Meade Julia , Schiff David , Walbert Tobias , Ambady Prakash , Bota Daniela A. , Campen Cynthia J. , Kaur Gurcharanjeet , Klesse Laura J. , Maraka Stefania , Moots Paul L. , Nevel Kathryn , Bornhorst Miriam , Aguilar-Bonilla Ana , Chagnon Sarah , Dalvi Nagma , Gupta Punita , Khatib Ziad , Metrock Laura K. , Nghiemphu P. Leia , Roberts Ryan D. , Robison Nathan J. , Sadighi Zsila , Stapleton Stacie , Babovic-Vuksanovic Dusica , Gershon Timothy R. ,   for the ReNeu Trial Investigators, Raslan Ahmed , Sidhu Alpa , Aguilar-Bonilla Ana , Franson Andrea T. , Walter Andrew , Hirbe Angela C. , Van Tine Brian , Koschmann Carl , Moertel Christopher L. , Campen Cynthia , Bota Daniela A. , Schiff David , Viskochil David , Babovic-Vuksanovic Dusica , Hajjar Fouad M. , Kaur Gurcharanjeet , Shuhaiber Hans H. , Capal Jamie K. , Slopis John , Gill Jonathan , Meade Julia , Nevel Kathryn , Metrock Laura K. , Bielamowicz Kevin , Klesse Laura J. , Weintraub Lauren , Nghiemphu Leia , Kilburn Lindsay , Mrugala Maciej M. , Schmidt Mary Lou , Bornhorst Miriam , Dalvi Nagma , Robison Nathan J. , Foreman Nick K. , Moots Paul L. , Ambady Prakash , Gupta Punita , Dhamija Radhika , McNall-Knapp Rene Y. , Antony Rueben , Roberts Ryan D. , Merrell Ryan , Chagnon Sarah , Stapleton Stacie , Maraka Stefania , Gershon Timothy R. , Walbert Tobias , Khatib Ziad , Sadighi Zsila 
Published: November 2024

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/m
2
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.