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

NCT03962543 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: MEK-NF-201
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 50

Brief 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.

Conditions

Plexiform Neurofibroma; Neurofibromatosis Type 1 (NF1)

Keywords

Neurofibromatosis; Neurofibromatosis 1; Plexiform Neurofibroma; PD-0325901; MEK Inhibitor; Neurofibroma; Mirdametinib

Outcome Measures

Primary Outcomes (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.

  Up to 24 months

Secondary Outcomes (5)

• Percentage of Patients With Treatment-Emergent Adverse Events.

  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.

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

  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

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

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

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

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

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

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

Other Outcomes (13)

• Change From Baseline in Localized Strength (Dynamometer) at Cycle 13.

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

• Change From Baseline in Range of Motion of PN-Associated Functional Impairment at Cycle 13.

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

• Change From Baseline in Endurance at Cycle 13.

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

Study Arms (1)

Mirdametinib (PD-0325901)

EXPERIMENTAL

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

Drug: Mirdametinib (PD-0325901) oral capsule or dispersible tablet

Interventions

Mirdametinib (PD-0325901) oral capsule or dispersible tablet DRUG

Mirdametinib (PD-0325901) capsule or dispersible tablet

Also known as: PD-0325901, Mirdametinib

Mirdametinib (PD-0325901)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany: lead

Study Sites (50)

University of Alabama at Birmingham/Children's of Alabama

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

UCLA Oncology Center

Los Angeles, California, 90095, United States

Location

University of California - Irvine Health

Orange, California, 92868-3201, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Lucile Packard Children's Hospital Stanford

Palo Alto, California, 94304, United States

Location

University of California - Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nemours A. I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida Clinical Research Center

Gainesville, Florida, 32610, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

AdventHealth Pediatric Oncology Hematology at Orlando

Orlando, Florida, 32804, United States

Location

Orlando Health, Inc.

Orlando, Florida, 32806, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Children's Healthcare of Atlanta - Center for Advanced Pediatrics

Atlanta, Georgia, 30329, United States

Location

University of Illinois Hospital and Health Systems

Chicago, Illinois, 60612, United States

Location

University of Chicago Medical Centers

Chicago, Illinois, 60637, United States

Location

IU Health Brain Tumor Infusion Clinic

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, 40202, United States

Location

University of Michigan CS Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine-Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

St. Joseph's Univeristy Medical Center

Paterson, New Jersey, 07503, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

UNC Medical Center

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

University of Oklahoma Health Sciences Center, Jimmy Everest Center for Cancer and Blood Disorders in Children

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Pittsburgh UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Henry-Joyce Cancer Clinic

Nashville, Tennessee, 37232, United States

Location

Children's Medical Center

Dallas, Texas, 75235, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah, Center for Clinical and Translational Sciences

Salt Lake City, Utah, 84108, United States

Location

UVA Health, Division of Neuro-Oncology

Charlottesville, Virginia, 22903, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23510, United States

Location

Swedish Medical Center - Cherry Hill Campus

Seattle, Washington, 98122, United States

Location

MACC Fund Research Center

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 39514826 DERIVED

MeSH Terms

Conditions

Neurofibroma, Plexiform; Neurofibromatosis 1; Neurofibromatoses; Neurofibroma

Interventions

mirdametinib

Condition Hierarchy (Ancestors)

Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Head of Clinical Operations
• Organization: SpringWorks Therapeutics, Inc.

clinical@springworkstx.com

8772794870

Study Officials

• Christopher L Moertel, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: 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.

Study Record Dates

• First Submitted: April 12, 2019
• First Posted: May 24, 2019
• Study Start: September 29, 2019
• Primary Completion: September 20, 2023
• Study Completion (Estimated): December 22, 2028
• Last Updated: May 6, 2026
• Results First Posted: August 7, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.

Locations

US (50)