Update on NF1 Research from SpringWorks Therapeutics

Author: SpringWorks Therapeutics
Published On: 03/22/2021

SpringWorks Therapeutics is currently conducting a clinical trial to study an investigational MEK inhibitor called mirdametinib in patients with Neurofibromatosis Type 1-associated plexiform neurofibromas (NF1-PN). The study, called the ReNeu trial, is an open label Phase 2b study in children (2 years or older) and adults with an inoperable NF1-PN. Mirdametinib is offered as an oral capsule or in a pediatric formulation for children who cannot swallow a capsule.  Participants will receive mirdametinib, which can be taken without regard to food, dosed at approximately 2mg/m2/dose (up to a maximum of 4mg twice a day) on 3 weeks on, 1 week off intermittent dosing schedule. The primary objective of this study is to evaluate the ability of mirdametinib to shrink the plexiform neurofibromas as measured by magnetic resonance imaging (MRI). Other key objectives include safety and tolerability as well as mirdametinib’s effect on physical functioning, quality of life, pain, and disfigurement.

More information on the ReNeu study can be found on the SpringWorks website or on www.clinicaltrials.gov under the identifier NCT03962543.


Below are answers to some questions you may have if you or your child is considering participation in this study.

Q. Has mirdametinib been used before in other people with NF1? 

Yes.  A Phase 2 study in 19 adolescent and adult patients with NF1-PN was conducted by the Neurofibromatosis Clinical Trials Consortium and was recently published in the Journal of Clinical Oncology (here is the link).  The study showed encouraging clinical activity in these patients, including a 42% objective response rate by course 12 of treatment.  The design of the ReNeu study was based on the results of this Phase 2 study.  As mentioned above, the ReNeu study is enrolling patients of all ages, including younger children (over the age of 2).

Q. What are the main side effects of mirdametinib?

Mirdametinib was generally well tolerated in the Phase 2 trial.   The most commonly reported treatment-related side effects in the Phase 2 trial were nausea, vomiting, rash, diarrhea, and fatigue. These are common side effects seen with MEK inhibitors in the NF1-PN patient population.  The ReNeu trial will be monitoring patients for these and all side effects.

Q. Could I get a placebo?

Everyone in the ReNeu study will receive mirdametinib; there is no placebo arm.

Q. How can I find out if my child or I qualify for the ReNeu Trial?

People who are interested in this study should discuss it with their doctor. Only a study doctor can determine if you or your loved one may meet the eligibility requirements.

Your doctor can find out more about the trial by searching for the NCT number NCT03962543 on clinicaltrials.gov, or he/she can email SpringWorks at clinical@springworkstx.com to get more information.

Q: How do I find the nearest ReNeu trial site to my home?

The ReNeu trial will be conducted in approximately 50 sites in the United States. Details of the trial locations can be found here.

Q: If I decide to participate, how long should I expect my participation to be?

Trial participation will last approximately 2 years.

Q: Are there any other ways for NF patients to access mirdametinib outside of this trial?

At this time mirdametinib is an investigational drug and whenever possible, use of an investigational therapy for a patient as part of a clinical trial is preferable because clinical trials are designed to generate comprehensive safety and efficacy data that may lead to the approval of the new medicine and, consequently, to wider availability for patients.

In cases where a clinical trial is not an option and the person has exhausted all available treatment options, and if the patient and their physician determine that mirdametinib may be of benefit, SpringWorks may be able to provide access through its Expanded Access Program if certain criteria are met.  Such a request would have to be initiated by your physician.  Information about SpringWorks’ Expanded Access Program can be found here.

Q. How is mirdametinib different from the other MEK inhibitor that was recently approved (selumetinib)?

Mirdametinib and selumetinib are both in the same class of drugs called MEK inhibitors. Whereas mirdametinib is an investigational drug not yet FDA approved, selumetinib has FDA approval for pediatric patients with plexiform neurofibromas and the statements made below reflect information from its approved label.  While they generally work in the same way, they are not the same drug and could have differences in both their efficacy and/or safety profile.  In addition, there are differences in how each medicine is dosed and taken.  For example, in the ReNeu study protocol, mirdametinib is given twice daily on a 3 week on, 1 week off schedule, whereas the FDA-approved label recommends that selumetinib be taken twice daily (approximately every 12 hours).  In addition, mirdametinib has a pediatric formulation for children who cannot swallow a capsule and can be taken in the ReNeu trial without regard to food, whereas the approved selumetinib label requires that food not be consumed for 2 hours before or 1 hour following each dose.

Patients are encouraged to speak with their physician regarding the differences between mirdametinib and selumetinib.


Anyone considering participating in a clinical trial should discuss the matter with his or her physician. If you or a loved one is interested in participating in NF research, please visit the "Participate in NF Research" section of our website to learn more about the clinical trial process and what that entails. 

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