A Study of Mirdametinib in Infants and Toddlers With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas

NCT07850635 | Not Yet Recruiting Phase 1 DMC

• 3 other identifiers: MEK-NF1-1042025-522000-24-002025
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety, pharmacokinetic (PK), and tolerability of multiple treatment cycles of oral mirdametinib in infants and toddlers (0 to less than \[\<\] 24 months of age) with measurable neurofibromatosis type 1 (NF1) associated plexiform neurofibromas (PNs) that is symptomatic or asymptomatic but in a high-risk location with a high risk of morbidity.

Conditions

Neurofibromatosis Type 1-Associated Plexiform Neurofibromas

Keywords

Mirdametinib; Single arm study

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  Up to approximately 6 years

• Number of Participants With Clinically Significant Changes in Laboratory Parameters, Vital Signs, Physical Examination Findings and Electrocardiograms (ECGs), Echocardiogram (ECHO), and Ophthalmic Exam Findings

  Up to approximately 6 years

• Number of Participants With Severity of Adverse Events (AEs) According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

  Up to approximately 6 years

• Minimum Observed Concentration (Cmin) of Mirdametinib

  Cycle 1 Days 1 and 15: pre-dose and post-dose at 1 and 4 hours; Cycles 2, 4 and 8 Day 15: Pre-dose and post-dose at 1 hour (each cycle = 28 days)

• Maximum Observed Concentration (Cmax) of Mirdametinib

  Cycle 1 Days 1 and 15: pre-dose and post-dose at 1 and 4 hours; Cycles 2, 4 and 8 Day 15: Pre-dose and post-dose at 1 hour (each cycle = 28 days)

• Area Under the Concentration-time Curve (AUC) at Steady State for Mirdametinib

  Cycle 1 Days 1 and 15: pre-dose and post-dose at 1 and 4 hours; Cycles 2, 4 and 8 Day 15: Pre-dose and post-dose at 1 hour (each cycle = 28 days)

Secondary Outcomes (4)

• Confirmed Objective Response Rate (ORR)

  Up to approximately 6 years

• Duration of Response (DoR)

  Up to approximately 6 years

• Change From Baseline in Quality of Life (QoL) Assessed by the age-specific Pediatric Quality of Life Inventory (PedsQL) Infant Scales

  Baseline up to approximately 6 years

• Change From Baseline Pain Assessment by Age-specific Pain Scale: Faces, Legs, Activity, Cry, Consolability (FLACC)

  Baseline up to approximately 6 years

Study Arms (2)

Cohort 1: 12 to 21 months of age

EXPERIMENTAL

Participant receives 0.5 milligram (mg) twice daily.

Drug: Mirdametinib

Cohort 2: 0 to 9 months of age

EXPERIMENTAL

Participants receives 0.25 mg twice daily.

Drug: Mirdametinib

Interventions

Mirdametinib DRUG

Mirdametinib dispersible tablet administered orally.

Cohort 1: 12 to 21 months of age; Cohort 2: 0 to 9 months of age

Eligibility Criteria

• Age: 0 Months - 21 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 1.1 Cohort 1: greater than (\>) 12 to less than or equal to (\<=) 21 months of age at first dose 1.2 Cohort 2: 0 to \<=9 months of age at first dose For both cohorts, corrected age must be used to determine eligibility for age at first dose. Note: Corrected age is the age of the infant from the expected date of delivery (40 weeks gestation), rather than from the actual date of birth. For example, a 3-month-old infant who was born 2 months early would have a corrected age of 1 month.
• Participants must have had the clinical diagnosis of NF1 according to the 2021 International Consensus Guidelines with presence of a PN and at least 1 additional diagnostic criterion for NF1.
• Participants must have a target PN, defined as the clinically most relevant PN amenable to volumetric MRI analysis. For the purpose of this study, the target PN must be seen on at least 3 consecutive MRI slices and the field of view must contain the entire tumour of interest. As determined by central radiologic review, a target PN must be analysable by volumetrics using Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS), at least 3 milliliter (mL) in volume.
• Participants must have 1 of the following presentations of PN:
• Asymptomatic: Participant has a measurable NF1 PN in a high risk location with a high risk of morbidity.
• A high-risk location with a high risk of morbidity is defined as:
• In the head or neck (except for isolated scalp lesions) OR
• Within the brachial or lumbosacral plexus OR
• Adjacent to high-risk structure(s), defined as:
• Major ("named") blood vessel OR
• Major ("named") airway OR
• Hollow viscus OR
• Spinal cord and foramina OR
• Vital organs (including heart, lungs, liver, spleen, etc) OR 4.2. Symptomatic: Participant has a PN that is causing clinical symptoms at the discretion of the investigator (e.g., head and neck lesions compromising the airway or great vessels, brachial or lumbar plexus lesions causing nerve compression and loss of function, lesions causing major deformity or significant disfigurement, lesions of the extremity causing limb hypertrophy or loss of function, and painful lesions).

You may not qualify if:

• Participant has family history of sudden cardiac death.
• Participant has a history of, or evidence of, retinal pathology on ophthalmologic examination that is considered a risk factor for central serous retinopathy, retinal vein occlusion (RVO), retinal pigment epithelial detachment, or neovascular macular degeneration.
• Participant has a history of congenital glaucoma.
• Participant has received NF1 PN-targeted therapy (e.g., farnesyltransferase inhibitors, kinase inhibitors, etc) within 28 days of first dose of study treatment (or 5 half-lives, whichever is longer). All toxicities from prior therapy must resolve to Grade \<=1 or baseline.
• Participant is receiving inhibitors or inducers of P-glycoprotein or breast cancer resistance protein.
• Participant is currently enrolled or has past participation in any other clinical study (excluding observational studies) within 28 days of signing of informed consent.

Sponsors & Collaborators

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

Study Sites (1)

Research Site

Darmstadt, Germany

Location

Related Links

• Trial Awareness and Transparency website

MeSH Terms

Interventions

mirdametinib

Study Officials

• Medical Responsible

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

  STUDY DIRECTOR

Central Study Contacts

Communication Center

CONTACT

+49 6151 72 5200; service@emdgroup.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2026
• First Posted: September 30, 2026
• Study Start (Estimated): December 10, 2026
• Primary Completion (Estimated): October 21, 2032
• Study Completion (Estimated): October 21, 2032
• Last Updated: September 30, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)