MEK Inhibitor for Neurofibromatosis

(ReNeu Trial)

Recruiting at 54 trial locations

Overseen By Senior Manager Clinical Operations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: SpringWorks Therapeutics, Inc.

Must not be taking: MEK1/2 inhibitors

Disqualifiers: Liver disease, Malignancy, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

114 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Mirdametinib (PD-0325901) for treating neurofibromatosis?

Research shows that MEK inhibitors, like Mirdametinib, have been effective in reducing tumor size in patients with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas. Similar drugs, such as Selumetinib, have shown a 68% response rate in children with NF1, leading to its FDA approval, and Mirdametinib has also proven effective in adults. ^{1 2 3 4 5}

Is the MEK inhibitor Mirdametinib safe for humans?

Mirdametinib, a MEK inhibitor, has been studied in clinical trials for neurofibromatosis type 1 and has shown a manageable safety profile, similar to other MEK inhibitors like selumetinib, which is FDA-approved for children with this condition. Common side effects of MEK inhibitors can include skin rashes and other skin-related issues, but these are generally manageable. ^{1 4 5 6 7}

How is the drug Mirdametinib different from other treatments for neurofibromatosis?

Mirdametinib is a MEK inhibitor that targets a specific pathway involved in the growth of plexiform neurofibromas, which are tumors associated with neurofibromatosis type 1. Unlike traditional treatments, it works by shrinking these tumors when surgery is not an option, offering a novel approach for managing this condition. ^{1 3 4 5 8}

What is the purpose of this trial?

This trial tests mirdametinib, a medication taken by mouth, for patients with NF1-related tumors that can't be surgically removed. The drug works by blocking specific proteins to stop or shrink the tumors. Mirdametinib has shown significant and lasting decreases in pain and partial responses in NF1-related plexiform neurofibromas.

Research Team

Christopher Moertel

Principal Investigator

University of Minnesota

Eligibility Criteria

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.

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.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Mirdametinib (PD-0325901) Experimental Treatment 1 Intervention

Mirdametinib (PD-0325901) capsule or dispersible tablet 2 mg/m\^2 (maximum dose of 4 mg) by mouth twice daily

Who Is Running the Clinical Trial?

SpringWorks Therapeutics, Inc.

Lead Sponsor

Trials

14

Recruited

900+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

A high-throughput drug sensitivity platform was used to analyze tumor cell lines from patients with Neurofibromatosis type 1 (NF1) and type 2 (NF2), revealing that NF1-associated tumors are particularly sensitive to MEK and ERK inhibitors.

The platform effectively predicted the outcomes of clinical trials for treating neurofibromas, suggesting it could be a valuable tool for developing targeted therapies for NF-related tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive pharmacological profiling of neurofibromatosis cell lines. Guo, J., Grovola, MR., Xie, H., et al.[2020]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Selumetinib in the Treatment of Neurofibromatosis Type 1-Related Plexiform Neurofibromas. Anderson, MK., Johnson, M., Thornburg, L., et al.[2022]

Selumetinib, a MEK inhibitor, has shown a remarkable overall response rate of 68% in children with neurofibromatosis type 1 (NF1) and symptomatic inoperable plexiform neurofibromas (PNs), leading to its FDA approval in May 2020.

Other targeted therapies, including cabozantinib and mirdametinib, have also demonstrated efficacy in adults with NF1, indicating a growing range of treatment options for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel molecular targeted therapies for patients with neurofibromatosis type 1 with inoperable plexiform neurofibromas: a comprehensive review. Solares, I., Viñal, D., Morales-Conejo, M., et al.[2021]

A young patient with neurofibromatosis type 1 (NF1) and recurrent glioblastoma showed a partial response to the MEK-inhibitor trametinib, but experienced significant cutaneous toxicity as a side effect.

Adding the BRAF-inhibitor dabrafenib to the treatment regimen helped alleviate the skin-related side effects, leading to a durable complete response and improved tolerance to the overall treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable Complete Response of a Recurrent Mesencephalic Glioblastoma Treated with Trametinib and Low-Dose Dabrafenib in a Patient with Neurofibromatosis Type 1. Awada, G., Serruys, D., Schwarze, JK., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Neurofibromatosis in the Era of Precision Medicine: Development of MEK Inhibitors and Recent Successes with Selumetinib. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Comprehensive pharmacological profiling of neurofibromatosis cell lines. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

A Review of Selumetinib in the Treatment of Neurofibromatosis Type 1-Related Plexiform Neurofibromas. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Novel molecular targeted therapies for patients with neurofibromatosis type 1 with inoperable plexiform neurofibromas: a comprehensive review. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Durable Complete Response of a Recurrent Mesencephalic Glioblastoma Treated with Trametinib and Low-Dose Dabrafenib in a Patient with Neurofibromatosis Type 1. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics and exposure-response of selumetinib and its N-desmethyl metabolite in pediatric patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas. [2021]

8. England pubmed.ncbi.nlm.nih.gov

MEK inhibitors - novel targeted therapies of neurofibromatosis associated benign and malignant lesions. [2021]