MEK Inhibitor for Neurofibromatosis

(ReNeu Trial)

Not currently recruiting at 58 trial locations
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Overseen BySenior Manager Clinical Operations
Age: Any Age
Sex: Any
Trial Phase: Phase 2
Sponsor: SpringWorks Therapeutics, Inc.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called mirdametinib (a MEK inhibitor) for individuals with neurofibromatosis type 1 (NF1), a genetic disorder that can cause tumors known as plexiform neurofibromas (PNs). The goal is to determine if this medication can reduce symptoms in those with tumors that cannot be surgically removed. Participants will take mirdametinib and may continue with long-term follow-up. This trial may suit individuals with NF1 who have troublesome tumors that cannot be fully removed by surgery and are willing to undergo MRIs and biopsies for study purposes. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have received NF1 PN-targeted therapy within 45 days, you may not be eligible to participate.

Is there any evidence suggesting that mirdametinib (PD-0325901) is likely to be safe for humans?

Research has shown that mirdametinib, a treatment for neurofibromatosis type 1 (NF1) with plexiform neurofibromas, has been studied for safety. In a previous study, adults taking mirdametinib experienced some side effects, but these were usually manageable. Common side effects included fatigue, nausea, and diarrhea, while serious side effects were less common.

Importantly, the FDA has already approved mirdametinib for treating both adults and children with NF1, indicating it has passed several safety checks for this condition. This approval suggests the treatment is considered safe for these groups. Prospective trial participants might find this existing information reassuring.12345

Why do researchers think this study treatment might be promising?

Mirdametinib is unique because it targets a specific pathway called the MEK/ERK pathway, which is often overactive in neurofibromatosis. Unlike standard treatments that might focus on managing symptoms or surgical options, Mirdametinib offers a targeted approach by directly inhibiting this pathway, potentially slowing or stopping the growth of tumors associated with the condition. Researchers are excited about this treatment because it could provide a more effective and less invasive option for patients, improving their quality of life by addressing the root cause of tumor growth.

What evidence suggests that mirdametinib might be an effective treatment for neurofibromatosis?

Research has shown that mirdametinib, the treatment under study in this trial, may help treat plexiform neurofibromas (PNs) associated with neurofibromatosis type-1 (NF1). In one study with 19 patients, about 42% experienced tumor shrinkage. Another study with 50 children found that 66% responded positively to the treatment. On average, it took about 5.4 months for half of the participants to notice these changes. Mirdametinib has been well-tolerated, with most people not experiencing serious side effects. These findings suggest that mirdametinib could effectively manage NF1-PNs.24567

Who Is on the Research Team?

Christopher L. Moertel | Medical School

Christopher Moertel

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for people with a condition called neurofibromatosis type-1 (NF1) and associated inoperable plexiform neurofibromas causing significant problems. Participants must have proper organ function, be willing to undergo tumor biopsies if they're adults, and their tumors should be measurable by MRI. They can't join if they've had certain recent treatments or severe health issues including heart disease, liver disease, infections, some cancers within the last 5 years, or are unable to tolerate MRI.

Inclusion Criteria

My organs and bone marrow are functioning well.
My tumor can be measured using MRI.
My peripheral nerve tumor cannot be fully removed by surgery.
See 6 more

Exclusion Criteria

I currently have an active infection.
I have had a serious illness or mental health condition in the past year.
I was diagnosed with breast cancer within the last 10 years.
See 10 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mirdametinib (PD-0325901) for the treatment of symptomatic inoperable neurofibromatosis type-1 associated plexiform neurofibromas

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up (optional)

Eligible participants may continue in a long-term follow-up phase

What Are the Treatments Tested in This Trial?

Interventions

  • Mirdametinib (PD-0325901)
Trial Overview The study tests mirdametinib (PD-0325901), given orally as a capsule or tablet, on patients with NF1-associated plexiform neurofibromas that cannot be surgically removed. Everyone in the study will receive this medication and may continue into a long-term follow-up phase to assess ongoing effects.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Mirdametinib (PD-0325901)Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

SpringWorks Therapeutics, Inc.

Lead Sponsor

Trials
14
Recruited
900+

Published Research Related to This Trial

Selumetinib, a MEK inhibitor, has shown significant efficacy in treating plexiform neurofibromas in patients with neurofibromatosis type 1, with 68% of 50 symptomatic patients experiencing a partial response and a median tumor volume reduction of 27.9%.
The treatment demonstrated a favorable safety profile, with manageable adverse effects, and resulted in an 84% estimated progression-free survival at 3 years, marking it as the first FDA-approved therapy for inoperable plexiform neurofibromas.
A Review of Selumetinib in the Treatment of Neurofibromatosis Type 1-Related Plexiform Neurofibromas.Anderson, MK., Johnson, M., Thornburg, L., et al.[2022]
In a phase II trial involving 19 patients with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs), the MAPK/ERK kinase inhibitor mirdametinib showed a 42% partial response rate after 12 courses, indicating its efficacy in reducing tumor size.
Patients reported significant and durable decreases in pain, suggesting that mirdametinib not only affects tumor volume but also improves quality of life for those suffering from NF1-related PNs.
NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas.Weiss, BD., Wolters, PL., Plotkin, SR., et al.[2022]
Selumetinib, a MEK inhibitor, is the first FDA-approved targeted therapy for neurofibromatosis type 1 (NF1), showing efficacy in treating inoperable plexiform neurofibromas, which are common and problematic tumors in NF1 patients.
Research into NF1 has advanced with better understanding of genetic and signaling pathways, leading to promising developments in combination therapies and new animal models that could enhance treatment options for other NF1-related conditions.
Neurofibromatosis in the Era of Precision Medicine: Development of MEK Inhibitors and Recent Successes with Selumetinib.Galvin, R., Watson, AL., Largaespada, DA., et al.[2022]

Citations

ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and ...In a phase II trial in 19 adults and adolescents with inoperable NF1-PN, eight (42%) patients achieved a partial response to mirdametinib by ...
NCT03962543 | MEK Inhibitor Mirdametinib (PD-0325901) ...This study evaluates mirdametinib (PD-0325901) in the treatment of symptomatic inoperable neurofibromatosis type-1 (NF1)-associated plexiform neurofibromas (PNs) ...
Press Release DetailsThe median time to an objective response was 5.4 months (range: 1.7 to 7.3). Mirdametinib was well-tolerated in the Phase 1 portion of the trial ...
Mirdametinib approval for neurofibromatosis type 1 with ...This approval was based on results from a trial of 50 pediatric patients, which showed an overall response rate of 66%. The trial also showed clinically ...
FDA approves mirdametinib for adult and pediatric patients ...The major efficacy outcome measure was confirmed overall response rate (ORR), defined as the percentage of patients with complete response ...
Adult NF1-PN Safety Profile - GOMEKLI.comView the GOMEKLI safety profile for adult patients with neurofibromatosis type 1 with plexiform neurofibromas, including information on adverse reactions.
Mirdametinib - NF1 TreatmentIndication and Important Safety Information About GOMEKLI · GOMEKLI (mirdametinib) is indicated for the treatment of adult and pediatric patients 2 years of age ...
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