A study of Mirdametinib in Infants and Toddlers under 24months of age with Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PNs)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Springworks Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16], Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-11-26

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

SpringWorks Therapeutics, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Pharmacokinetic

To evaluate the safety, tolerability, and pharmacokinetics (PK) of mirdametinib in infants and toddlers (0 to <24 months) with measurable NF1 PNs who are symptomatic or are asymptomatic but have disease in a high-risk location with a high risk of morbidity.

Secondary objectives 4

1. To evaluate the confirmed complete and partial response rate at the end of the Treatment Phase using volumetric magnetic resonance imaging (MRI) analysis.
2. To determine the duration of response (DoR).
3. To evaluate the effect of mirdametinib on quality of life (QoL) as measured by parent proxy-reported outcome assessments.
4. To evaluate the effect of mirdametinib on pain as measured by clinician assessments.

Conditions and MedDRA coding

Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN)

Study design 2 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003525-PIP01-23

Plan to share IPD

Yes

IPD plan description

SpringWorks is committed to data transparency and sharing data to further research while maintaining the privacy and confidentiality of research participants. Pertinent patient-level data from clinical trials will be made available by SpringWorks to qualified researchers upon approval of reasonable requests following de-identification/anonymization pursuant to applicable law

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age 1.1. Cohort 1: ≥12 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.
2. 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
3. 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 REiNS, at least 3 mL in volume.
4. Participants must have 1 of the following presentations of PN: 4.1. Asymptomatic: Participant has a target 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: o Major (“named”) blood vessel OR o Major (“named”) airway OR o Hollow viscus OR o Spinal cord and foramina OR o 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).

Exclusion criteria 6

1. Participant has family history of sudden cardiac death
2. 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
3. Participant has a history of congenital glaucoma
4. 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.
5. Participant is receiving inhibitors or inducers of P-glycoprotein or breast cancer resistance protein
6. Participant is currently enrolled or has past participation in any other clinical study (excluding observational studies) within 28 days of signing of informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Key safety endpoints will include incidence of TEAEs, changes in laboratory parameters, vital signs, physical examination findings and electrocardiograms (ECGs), echocardiogram (ECHO), and ophthalmic exam findings
2. The severity of all AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
3. PK parameters, such as Cmin, Cmax, and AUC at steady state.

Secondary endpoints 4

1. Confirmed ORR (defined as PN decrease ≥20% compared to baseline in consecutive scans within 2 to 6 months) using centrally read MRI volumetric analyses by a Blinded Independent Central Review (BICR).
2. DoR, defined as the time from onset of confirmed complete response (CR) + partial response (PR) using centrally read MRI volumetric analysis by a BICR to the earliest event of progressive disease (PD) or death.
3. Change from baseline in QoL assessed by the age-specific Paediatric Quality of Life Inventory (PedsQL) Infant Scales.
4. Change from baseline pain assessment by age-specific pain scale: faces, legs, activity, cry, consolability (FLACC)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Springworks Therapeutics Inc.

Sponsor organisation

Springworks Therapeutics Inc.

Address

100 Washington Boulevard

City

Stamford

Postcode

06902-9302

Country

United States

Scientific contact point

Organisation

Springworks Therapeutics Inc.

Contact name

Michael Weber

Public contact point

Organisation

Springworks Therapeutics Inc.

Contact name

SpringWorks Clinical

Third parties 11

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications