Mirdametinib Demonstrates Durable Responses in NF1-Associated Plexiform Neurofibromas

Key Clinical Summary:

• Design/Population: The phase 2 ReNeu trial evaluated mirdametinib in 114 adult and pediatric patients with NF1-associated, symptomatic, inoperable plexiform neurofibromas, treated in 28-day cycles with optional long-term follow-up.
• Key Outcomes: Confirmed ORR was 47% in adults and 55% in children, with deep responses (>50% tumor reduction) observed in both cohorts. Median tumor volume reduction was ~40% in both groups, and duration of response was not reached. Grade ≥3 treatment-related adverse events occurred in 17% of adults and 25% of children, with no new safety signals.
• Clinical Relevance: Mirdametinib provides durable and clinically meaningful tumor shrinkage in NF1-PN across age groups, with an acceptable safety profile, supporting its role as a standard systemic therapy for patients with symptomatic, unresectable disease.

Angela Hirbe, MD, PhD, Washington University, St. Louis, Missouri, discusses long-term follow-up results from the phase 2b ReNeu trial evaluating mirdametinib among adult and pediatric patients with inoperable, symptomatic neurofibromatosis type 1 (NF1)-associated plexiform neurofibromas. 

Results demonstrated that mirdametinib improved objective response rates with additional deep responses in this patient population, with a consistent safety profile supporting sustained clinical benefit with continued treatment.

Dr Hirbe presented these results at the 2026 European Society of Medical Oncology (ESMO) Sarcoma and Rare Cancers Congress in Lugano, Switzerland. 

Transcript:

Hi there, my name is Angela Hirbe and I am an associate professor of medicine and pediatrics and director of the adult neurofibromatosis clinical program at Washington University in St. Louis.

I had the honor of presenting an update from the long-term follow-up phase of the ReNeu study, a pivotal phase 2b trial of mirdametinib in adults and children with neurofibromatosis type 1 (NF1)-associated symptomatic plexiform neurofibromas.

Plexiform neurofibromas are benign nerve sheath tumors that occur in almost half of patients with NF1 and these tumors can lead to very significant pain, disfigurement, neurologic deficits, and impaired quality of life. The previously published phase 2b ReNeu trial met its primary end point of confirmed overall response rate in adults and children with NF1-associated plexiform neurofibromas and reported deep and durable reductions in target plexiform neurofibroma volume, as well as early, sustained, and meaningful improvements in quality of life. Mirdametinib became the first MEK1/2 inhibitor approved by the US FDA, as well as by the European Commission, for both adults and children 2 years of age and older with NF1 who have symptomatic plexiform neurofibromas. What we reported here were results from the long-term follow-up phase of this study.

Patients with inoperable plexiform neurofibromas were enrolled into 2  cohorts based on age, 58 adults and 56 children ages 2 to 17 years. They received mirdametinib 2 mg/m² twice daily 3 weeks on and 1 week off, with each cycle being 28 days. We reported an additional 9 months of data from the initial September 20, 2023 data cutoff.

From the waterfall plots, we observed very deep responses in the adult cohort and with the additional 9 months of data we had 1 additional patient with a confirmed objective response and 3 additional patients who achieved deep responses, defined as greater than 50% reductions in tumor volume. From the swimmer plots, we were also able to show that these responses were very durable. Interestingly, the median time to onset of response increased by 1.7 months in the adult cohort and the time to best percentage change increased by 2.3 months, indicating that with longer follow-up more responses were observed and responses deepened over time. 

Very similar findings were seen in the pediatric cohort. There was an additional patient with an objective response and 4 additional patients with deep responses, again defined as greater than 50% reduction in tumor volume. The swimmer plots similarly demonstrated durable responses. The median time to best percentage change increased by 1.7 months in the pediatric cohort. 

Importantly, in both cohorts, the median duration of response has not yet been reached. There were no additional treatment-related adverse events observed in the long-term follow-up phase.

The bottom line is that mirdametinib demonstrated improvement over time in confirmed objective responses assessed by blinded independent central review, leading to an objective response rate of 47% in adults and 55% in pediatric patients. Deep responses, defined as greater than 50% reduction in plexiform neurofibroma volume, were achieved in the majority of patients—67% of adults and 61% of children. These responses were durable at the time of data cutoff, observed in 96% of adult responders and 100% of pediatric responders, with a very manageable safety profile. Most treatment-related adverse events were grade 1/2, and no new safety signals emerged.

Overall, with longer mirdametinib treatment, more patients achieved confirmed objective responses, and additional deep responses were observed, with no new safety signals emerging. 

Source: 

Hirbe A, Shuhaiber H, Viskochil D, et al. Update from the long-term follow-up (LTFU) phase of ReNeu: A pivotal phase IIb trial of mirdametinib in adults and children with neurofibromatosis type 1 (NF1)-associated symptomatic plexiform neurofibroma (PN). Presented at ESMO Sarcoma and Rare Cancers. March 12 - 14, 2026; Lugano, Switzerland. 288MO.