Abstract Details

Title ReNeu: A Pivotal Phase 2b Trial of Mirdametinib in Children and Adults With Neurofibromatosis Type 1 (NF1)-Associated Symptomatic Plexiform Neurofibroma (PN)

Topic Neuro-oncology

Presentation(s) S29 - Neuro-oncology (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Background

Pharmacologic therapies for NF1-PN are limited.

Objective ReNeu (NCT03962543) is a pivotal, phase 2b trial evaluating efficacy and safety of mirdametinib (investigational MEK1/2 inhibitor) in adults and children (≥2y) with symptomatic inoperable NF1-PN.

Design/Methods Patients received mirdametinib capsule or dispersible tablet (2mg/m² BID, max 4mg BID, 3-weeks-on/1-week-off 28-d cycles). Primary endpoint was confirmed objective response rate (ORR; proportion of patients with ≥20% reduction of target PN volume by MRI on consecutive scans within 2-6mo during 24-cycle treatment phase assessed by blinded independent central review [BICR]); minimum clinically relevant ORR (null) defined as 23% (adults), 20% (children). Patients could continue treatment in a long-term follow-up (LTFU) phase.

Results Fifty-eight adults and 56 children received mirdametinib. As of data cutoff (20-Sept-2023), BICR-confirmed ORR (95%CI) was 41% (29%, 55%; P<.001) in adults and 52% (38%, 65%; P<.001) in children. Two adults and 1 child also had confirmed response in the LTFU. Median (range) target PN volumetric best response from baseline was -41% (-90%, 13%) in adults, -42% (-91%, 48%) in children. Median treatment duration was 22mo for both cohorts; median duration of response was not reached. Median (range) time to response was 7.8mo (4-19mo) in adults, 7.9mo (4-19mo) in children. Patients or parents reported significant improvements from baseline to Cycle 13 in worst tumor pain severity, pain interference, and health-related quality-of-life measures. Most frequent (≥25% patients) treatment-related adverse events (TRAEs) were dermatitis acneiform, diarrhea, nausea, and vomiting in adults; and dermatitis acneiform, diarrhea, and paronychia in children. Grade ≥3 TRAEs were reported by 16% and 25% of adults and children, respectively; 21% and 9% of adults and children, respectively, discontinued due to TRAEs.

Conclusions Mirdametinib demonstrated deep and durable tumor responses, significant improvement in pain and HRQoL, and manageable safety in adults and children, underscoring mirdametinib’s potential to become an important new NF1-PN treatment option.

Authors/Disclosures
Phioanh L. Nghiemphu, MD, FAAN (UCLA Neuro-Oncology) PRESENTER	Dr. Nghiemphu has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Simpson Healthcare. Dr. Nghiemphu has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Nghiemphu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Springswork. Dr. Nghiemphu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CIRM. Dr. Nghiemphu has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Springworks. The institution of Dr. Nghiemphu has received research support from Erasca. The institution of Dr. Nghiemphu has received research support from Springswork. The institution of Dr. Nghiemphu has received research support from Children's Tumor Foundation. The institution of Dr. Nghiemphu has received research support from NIH-NCI . The institution of Dr. Nghiemphu has received research support from DOD. The institution of Dr. Nghiemphu has received research support from GCAR.
Hans H. Shuhaiber, MD	The institution of Dr. Shuhaiber has received research support from SPRINGWORKS . The institution of Dr. Shuhaiber has received research support from RECURSION . The institution of Dr. Shuhaiber has received research support from AstraZeneca. The institution of Dr. Shuhaiber has received research support from CTF. The institution of Dr. Shuhaiber has received research support from NFLECTION .
Christopher L. Moertel, MD	Dr. Moertel has received personal compensation for serving as an employee of OX2 Therapeutics. Dr. Moertel has received personal compensation for serving as an employee of Alexion . Dr. Moertel has received personal compensation for serving as an employee of Springworks. Dr. Moertel has stock in OX2 Therapeutics. Dr. Moertel has received intellectual property interests from a discovery or technology relating to health care.
Angela Hirbe, MD, PhD	Dr. Hirbe has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SpringWorks Therapeutic. Dr. Hirbe has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Hirbe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aadi Subsidiary Inc. The institution of Dr. Hirbe has received research support from Tango. Dr. Hirbe has received intellectual property interests from a discovery or technology relating to health care.
David Viskochil, MD, PhD (University of Utah)	The institution of David Viskochil, MD, PhD has received research support from Astellas. The institution of David Viskochil, MD, PhD has received research support from Takeda. The institution of David Viskochil, MD, PhD has received research support from Springworks. The institution of David Viskochil, MD, PhD has received research support from NFlection.
Alpa o. Sidhu, MBBS, PhD	The institution of Dr. Sidhu has received research support from SpringWorks Therapeutics.
Kevin Bielamowicz (UAMS/Arkansas Children's Hospital)	Kevin Bielamowicz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion Pharmaceuticals. Kevin Bielamowicz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Springworks Therapeutics. Kevin Bielamowicz has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion Pharmaceuticals.
Michael D. Weber, PharmD	Dr. Weber has received personal compensation for serving as an employee of SpringWorks Therapeutics. Dr. Weber has stock in SpringWorks Therapeutics.
Armend Lokku, PhD	Dr. Lokku has nothing to disclose.
L Mary M. Smith, PhD	Dr. Smith has received personal compensation for serving as an employee of SpringWorks Therapeutics Inc. Dr. Smith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for SpringWorks Therapeutics. Dr. Smith has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for Lifordi Immunotherapeutics.
Lauren Weintraub, MD	Dr. Weintraub has nothing to disclose.
Rene Y. McNall-Knapp, MD	The institution of Dr. McNall-Knapp has received research support from SpringWorks. The institution of Dr. McNall-Knapp has received research support from Alexion. The institution of Dr. McNall-Knapp has received research support from Pfizer.
FOUAD M. HAJJAR, MD	Dr. HAJJAR has nothing to disclose.
Nicholas K. Foreman, MD	Prof. Foreman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Georgia University.
Timothy R. Gershon, MD, PhD (University of North Carolina At Chapel Hill)	No disclosure on file
Dusica babovic-vuksanovic, MD	Dr. babovic-vuksanovic has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AstraZeneca/Alexion. Dr. babovic-vuksanovic has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SpringWorks. Dr. babovic-vuksanovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. babovic-vuksanovic has received research support from SprinWorks. Dr. babovic-vuksanovic has received publishing royalties from a publication relating to health care. Dr. babovic-vuksanovic has received personal compensation in the range of $500-$4,999 for serving as a USMLE items review with NBME.

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