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Plexiform NeurofibromaPhase 2ReNeuNCT03962543

MEK Inhibitor Mirdametinib (PD-0325901) in Patients With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas

A Phase 2 study testing Mirdametinib (PD-0325901) oral capsule or dispersible tablet in people with Plexiform Neurofibroma and Neurofibromatosis Type 1 (NF1), run by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany at 43 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This study evaluates mirdametinib (PD-0325901) in the treatment of symptomatic inoperable neurofibromatosis type-1 (NF1)-associated plexiform neurofibromas (PNs). All participants will receive mirdametinib (PD-0325901). Eligible participants may continue in a long-term follow-up phase. Read more about this study

Who is it for?
Ages 2 years and older
What is being tested?
Mirdametinib (PD-0325901) oral capsule or dispersible tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
114 participants
Where
43 sitesUnited States
Study dates
29 Sep 2019to 22 Dec 2028
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Participant has documented NF1 mutation or a diagnosis of neurofibromatosis type 1 (NF1) using National Institute of Health (NIH) Consensus Conference criteria inclusive of the presence of a plexiform neurofibroma (PN).
  • Participant has a PN that is causing significant morbidity.
  • Participant has a PN that cannot be completely surgically removed.
  • Participant has a target tumor that is amenable to volumetric MRI analysis.
  • Participant is willing to undergo a tumor biopsy pre and post treatment if ≥ 18 years of age.
  • Participant has adequate organ and bone marrow function.

Who cannot join

  • Participant has abnormal liver function or history of liver disease.
  • Participant has lymphoma, leukemia or any malignancy within the past 5 years (except for resected basal/squamous skin carcinomas without metastases within 3 years).
  • Participant has breast cancer within 10 years.
  • Participant has active optic glioma or other low-grade glioma requiring treatment.
  • Participant has abnormal QT interval corrected or other heart disease within 6 months.
  • Participant has a history of retinal pathology, risk factors for retinal vein occlusion or has a history of glaucoma.
Show all 13Show fewer
  • Participant has known malabsorption syndrome or gastrointestinal conditions that would impair absorption of mirdametinib (PD-0325901).
  • Participant has received NF1 PN-targeted therapy within 45 days.
  • Participant previously received or is currently receiving therapy with mirdametinib (PD-0325901) or any other MEK1/2 inhibitor.
  • Participant has received radiation therapy within 6 months or has received radiation to the orbit at any time.
  • Participant is unable to undergo or tolerate MRI.
  • Participant has active bacterial, fungal or viral infection.
  • Participant has experienced other severe acute or chronic medical or psychiatric conditions within 1 year.

Trial locations and contacts

43 sites in 1 country.

43 sites in 1 country

United States43 sites

  • Albany Medical Center

    Albany, New York, 12208

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • University of Alabama at Birmingham (UAB) - Children's of Alabama

    Birmingham, Alabama, 35233

  • University of North Carolina (UNC) Hospitals

    Chapel Hill, North Carolina, 27599

  • University of Virginia - Emily Couric Cancer Center

    Charlottesville, Virginia, 22903

  • University of Illinois Hospital

    Chicago, Illinois, 60612

  • UC Health

    Cincinnati, Ohio, 45229

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • University of Texas Southwestern

    Dallas, Texas, 75244

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • University of Florida (UF) - Gainesville

    Gainesville, Florida, 32610

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • University of Iowa Health Care

    Iowa City, Iowa, 52242

  • Arkansas Children's Hospital - University of Arkansas

    Little Rock, Arkansas, 72202

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • University of California, Los Angeles (UCLA)

    Los Angeles, California, 90095

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • University of Minnesota Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • Vanderbilt Children's Hospital

    Nashville, Tennessee, 37232

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23510

  • University of Oklahoma - Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital of Orange County

    Orange, California, 92868

  • University of California - Irvine Health

    Orange, California, 92868

  • Florida Hospital Cancer Institute

    Orlando, Florida, 32804

  • Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

  • UPMC Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15219-2739

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California - Davis

    Sacramento, California, 95817

  • The University of Utah Health Sciences Center

    Salt Lake City, Utah, 84108

  • Washington University

    St Louis, Missouri, 63110

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • Moffitt

    Tampa, Florida, 33612

  • Children's Hospital at Montefiore

    The Bronx, New York, 10467

  • Children's National Hospital

    Washington D.C., District of Columbia, 20010

  • Nemours A. I. duPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

About this study

Official title: A Phase 2b Trial of the MEK 1/2 Inhibitor (MEKi) PD-0325901 in Adult and Pediatric Patients With Neurofibromatosis Type 1 (NF1)-Associated Inoperable Plexiform Neurofibromas (PNs) That Are Causing Significant Morbidity

This study evaluates mirdametinib (PD-0325901) in the treatment of symptomatic inoperable neurofibromatosis type-1 (NF1)-associated plexiform neurofibromas (PNs). All participants will receive mirdametinib (PD-0325901). Eligible participants may continue in a long-term follow-up phase.

Read the detailed description

Neurofibromas are non-malignant peripheral nerve sheath tumors, which are classified as plexiform neurofibromas (PNs) if they extend longitudinally along a nerve and involve multiple fascicles. PNs are a major cause of morbidity and disfigurement in individuals with NF1, and as the tumor growth progresses, can cause a multitude of clinical problems including pain and impaired physical function. PNs have the potential to undergo malignant transformation to Malignant Peripheral Nerve Sheet Tumors (MPNST).

Mirdametinib (PD-0325901) is an orally delivered, highly selective small-molecule inhibitor of the dual specificity kinases, MEK1 and MEK2 (MAPK/ERK Kinase) which prevents the phosphorylation and subsequent activation of mitogen-activated protein kinase (MAPK).

Previous studies of mirdametinib (PD-0325901) demonstrated PN shrinkage and sustained inhibition of pERK. Reduced tumor volume indicated that cell proliferation or cell death may be altered in PNs with administration of mirdametinib (PD-0325901).

Being tested
Mirdametinib (PD-0325901) oral capsule or dispersible tablet
Keywords
Neurofibromatosis, Neurofibromatosis 1, Plexiform Neurofibroma, PD-0325901, MEK Inhibitor, Neurofibroma, Mirdametinib
Medical subject headings
Neurofibroma, Plexiform, Neurofibromatosis 1, Neurofibromatoses, Neurofibroma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mirdametinib (PD-0325901) oral capsule or dispersible tabletDrug

    Also called PD-0325901, Mirdametinib

    Mirdametinib (PD-0325901) capsule or dispersible tablet

Study groups in NCT03962543
Study groupRoleWhat they receive
Mirdametinib (PD-0325901)ExperimentalMirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m^2 (maximum dose of 4 mg) by mouth twice daily
Receives: Drug: Mirdametinib (PD-0325901) oral capsule or dispersible tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Confirmed Objective Response Rate at the End of the Treatment Phase.

    Response will be determined by a blinded centralized review of volumetric MRI. The confirmed objective response rate (complete or partial response) by the end of Treatment Phase (i.e., Cycle 24) is defined as the proportion of participants who have a confirmed ≥ 20% reduction in target tumor volume as compared to baseline as assessed by a BICR, and the response needs to be confirmed by BICR in a consecutive tumor assessment within 2 - 6 months. Partial response is defined as a ≥ 20% reduction in target tumor volume from baseline. Complete response is defined as the complete resolution of the target tumor.

    Measured: Up to 24 months

Secondary outcomes (5)

  1. Percentage of Patients With Treatment-Emergent Adverse Events.

    All adverse events were coded using MedDRA Version 24.0. Adverse events will be assessed according to toxicities graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

    Measured: All SAEs and AEs were collected from the time of signing ICF until 30 days after the last dose of study treatment, an average of 1 year and 10 months and up to 3 years and 10 months.

  2. Duration of Response (DOR) for Participants Who Meet Criteria for Confirmed Objective Response.

    Duration of response is defined as the time in months between the first instance of response that is subsequently confirmed, until the date of radiographic disease progression or death, whichever occurs first. For participants who enter the LTFU Phase, all MRI assessments in both the Treatment Phase and LTFU Phase will be used to determine duration of response. Participants without radiographic disease progression or death while on study will have their results censored to their most recent adequate (i.e. evaluable) tumor assessment date.

    Measured: Starting on the onset of confirmed objective response in the Treatment Phase and afterwards on the 15th day of every 4 cycles (each cycle is 28 days) until disease progression or death, whichever comes first, assessed up to approximately 3 years

  3. Change From Baseline on Quality of Life (QOL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) at Cycle 13, Acute Version.

    The PedsQL consists of a 23-item core measure of global QOL that can be completed in approximately 5 minutes. There is a total score and four subscales: physical functioning, emotional functioning, social functioning and school/work functioning. Participants ≥ 5 years of age complete an age-appropriate self-report; and parents/guardians of children ages 2-17 complete a parent proxy report of the age-specific QOL. The recall period is 7 days. PedsQL items are answered on a Likert scale with responses ranging from 0 to 4 (where 0 means it is never a problem and 4 means it is almost always a problem). These items are then reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. On this scale, higher scores indicate better outcomes. Overall scale scores are calculated as the mean of the scores for the questions in said scale (or of all questions for the total score). The change from baseline is modelled using a mixed-model for repeated measures.

    Measured: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months

  4. Change From Baseline in Pain as Measured by the Numeric Rating Scale-11 (NRS-11) at Cycle 13.

    The NRS-11 is a self-reported 11-point numerical scale that assesses pain severity. Participants ≥ 8 years of age are asked to select a number from 0 (no pain) to 10 (worst pain you can imagine) that best describes their worst pain. The recall period is 24 hours. The change from baseline is modelled using a mixed-model for repeated measures.

    Measured: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months

  5. Change From Baseline in Pain as Measured by the Pain Interference Index (PII) at Cycle 13.

    The PII assesses relevant aspects of one's life, including pain interference with activities, spending time with family/friends, mood, sleep and attention. Participants ≥ 6 years of age complete a self-report, and parents/guardians of children aged 6-17 complete a parent proxy report. The recall period is 24 hours. The PII consists of 6 questions, each asking the responder to select one number from 0 to 6 that best describes how their/their proxy's pain has impacted various items over the past 24 hours with 0 representing "Not at all" and 6 representing "Completely". The mean of the completed items is taken as the PII score for a single assessment. The PII score presented each visit will be taken as the average of the PII scores over the 7 consecutive days up to and including visit day, with no transformation applied. The change from baseline is modelled using a mixed-model for repeated measures.

    Measured: Baseline and Cycle 13 (1 cycle = 28 days), up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2019
  2. Study start29 Sep 2019
  3. Primary completion20 Sep 2023
  4. Study completion22 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
All participants will receive mirdametinib (PD-0325901) at a dose of 2 mg/m\^2 twice daily (maximum dose of 4 mg twice daily), calculated based on body surface area. Dose will be administered in a 3-week on, 1-week off schedule.
Masking
None (open label)
Enrolment
114 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03962543
Sponsor's protocol ID
MEK-NF-201
Acronym
ReNeu
Status last verified
Sep 2026
First submitted
12 Apr 2019
Last updated
6 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD supporting publicly available results will be evaluated for sharing.
Expanded access
Available

Publications

  • Hirbe A, Moertel CL, Babovic-Vuksanovic D, Rohl C, Bischoff K, Kelts K, Langseth AJ, Weber MD, Oberlander B, Wunderlich A, Jared J, Gershon TR. Plain language summary of the ReNeu study: a study of mirdametinib for adults and children with neurofibromatosis type 1 (NF1) who have plexiform neurofibromas. Future Oncol. 2026 Oct 29:1-21. doi: 10.1080/14796694.2026.2722495. Online ahead of print.

    PubMed 42954271

  • Moertel CL, Hirbe AC, Shuhaiber HH, Bielamowicz K, Sidhu A, Viskochil D, Weber MD, Lokku A, Smith LM, Foreman NK, Hajjar FM, McNall-Knapp RY, Weintraub L, Antony R, Franson AT, Meade J, Schiff D, Walbert T, Ambady P, Bota DA, Campen CJ, Kaur G, Klesse LJ, Maraka S, Moots PL, Nevel K, Bornhorst M, Aguilar-Bonilla A, Chagnon S, Dalvi N, Gupta P, Khatib Z, Metrock LK, Nghiemphu PL, Roberts RD, Robison NJ, Sadighi Z, Stapleton S, Babovic-Vuksanovic D, Gershon TR; ReNeu Trial Investigators; ReNeu Study Investigators. ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma. J Clin Oncol. 2025 Feb 20;43(6):716-729. doi: 10.1200/JCO.24.01034. Epub 2024 Nov 8.

    PubMed 39514826

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Mirdametinib (PD-0325901) oral capsule or dispersible tablet in people with Plexiform Neurofibroma and Neurofibromatosis Type 1 (NF1), run by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany at 43 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Confirmed Objective Response Rate at the End of the Treatment Phase. (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03962543, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.

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