Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas

NCT04924608 | Active Not Recruiting Phase 3 Results FDA Drug

• 2 other identifiers: D134BC000012020-005607-39
• Study Type: interventional
• Target: 145
• Locations: 13 countries
• Sites: 34

Brief Summary

A global study to demonstrate the effectiveness of selumetinib in participants with NF1 who have symptomatic, inoperable plexiform neurofibromas.

Conditions

Neurofibromatosis 1; Plexiform Neurofibroma (PN)

Keywords

Neurofibromatosis Type 1; NF1; Plexiform Neurofibroma (PN); PNs; Selumetinib; MEK inhibitor

Outcome Measures

Primary Outcomes (1)

• Confirmed Partial and Complete Response Rate (ORR) by End of Cycle 16 Using Volumetric MRI Analysis as Determined by ICR (Per REiNS Criteria) in Participants With NF1 Who Have Symptomatic, Inoperable PN.

  Objective response rate is defined as the proportion of participants who have a confirmed CR (defined as disappearance of the target PN, confirmed by a consecutive scan within 3 to 6 months after the first response) or confirmed PR (defined as a target PN volume decrease ≥ 20%, compared to baseline, confirmed by a consecutive scan within 3 to 6 months after the first response) by end of Cycle 16 as determined by ICR per REiNS criteria. Increase in the volume of the target PN by 20% or more compared to baseline or the time of best response after documenting a PR is considered as PD.

  From first dose up until progression (if it occurs prior to the end of Cycle 16), or the last evaluable assessment up to and including the end of Cycle 16, excluding MRI during prolonged study intervention interruption (defined as interruption >= 28 days)

Secondary Outcomes (3)

• (First Key Secondary) The Difference of the Means in the Change From Baseline in PAINS-pNF Chronic Target PN Pain Intensity Score at Cycle 12 Between Selumetinib and Placebo, Primary Analysis

  Baseline and end of cycle 12 of study intervention

• (First Key Secondary) The Difference of the Means in the Change From Baseline in PAINS-pNF Chronic Target PN Pain Intensity Score at Cycle 12 Between Selumetinib and Placebo, Supplemental Analysis

  Baseline and end of cycle 12 of study intervention

• (Second Key Secondary Endpoint) The Difference of the Means in the Change From Baseline in PlexiQoL Total Score at Cycle 12

  Baseline and end of Cycle 12 of study intervention

Study Arms (2)

Arm A

EXPERIMENTAL

Selumetinib

Drug: Selumetinib

Arm B

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Selumetinib DRUG

Selumetinib oral capsules (10 mg and 25 mg)

Also known as: AZD6244

Arm A

Placebo OTHER

Placebo oral capsules for Selumetinib masking (10 mg and 25 mg)

Arm B

Eligibility Criteria

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

You may qualify if:

• Adults ≥ 18 years at enrollment with diagnosis of NF1 with symptomatic, inoperable PN
• At least one inoperable target PN measurable by volumetric MRI analysis
• Chronic target PN pain score documented for minimum period during screening period
• Stable chronic PN pain medication use at enrollment
• Adequate organ and marrow function

You may not qualify if:

• History of malignancy except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention and of low potential risk for recurrence
• Clinically significant cardiovascular disease, including inherited coronary disease, acute coronary syndrome within 6 months prior to enrollment, uncontrolled angina, symptomatic heart failure, cardiomyopathy, severe valvular heart disease, abnormal LVEF and uncontrolled hypertension
• Ophthalmological findings/conditions including intraocular pressure \> 21 mmHg, RPED/CSR or RVO
• Prior exposure to MEK inhibitors

Sponsors & Collaborators

• AstraZeneca: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (34)

Research Site

Gainesville, Florida, 32610, United States

Location

Research Site

Rockville, Maryland, 20852, United States

Location

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St Louis, Missouri, 63156, United States

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Commack, New York, 11725, United States

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Melbourne, 3000, Australia

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St Leonards, 2065, Australia

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Porto Alegre, 90035-903, Brazil

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Ribeirão Preto, 14051-140, Brazil

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São Paulo, 045202-001, Brazil

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Toronto, Ontario, M5G 2C4, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Beijing, 100070, China

Location

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Beijing, 100730, China

Location

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Guangzhou, 510060, China

Location

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Shenyang, 110001, China

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Créteil, 94000, France

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Lyon, 69008, France

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Toulouse, 31059, France

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Hamburg, 20246, Germany

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Tübingen, 72076, Germany

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Würzburg, 97080, Germany

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Milan, 20133, Italy

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Naples, 80131, Italy

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Roma, 00165, Italy

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Minatoku, 105-8471, Japan

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Nagoya, 466-8560, Japan

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Shinjuku-ku, 160-8582, Japan

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Bydgoszcz, 85-094, Poland

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Moscow, 115522, Russia

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Moscow, 125412, Russia

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Badalona, 08916, Spain

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Madrid, 28041, Spain

Location

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London, SE1 9RT, United Kingdom

Location

Research Site

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• Chen AP, Coyne GO, Wolters PL, Martin S, Farschtschi S, Blanco I, Chen Z, Darrigo LG Jr, Eoli M, Whittle JR, Nishida Y, Lamarca R, de la Rosa Rodriguez R, Adeyemi A, Herrero I, Llorente N, Diede SJ, Dombi E, Wolkenstein P; KOMET study investigators. Efficacy and safety of selumetinib in adults with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas (KOMET): a multicentre, international, randomised, placebo-controlled, parallel, double-blind, phase 3 study. Lancet. 2025 Jun 21;405(10496):2217-2230. doi: 10.1016/S0140-6736(25)00986-9. Epub 2025 Jun 2.

  PMID: 40473450 DERIVED

Related Links

• Redacted Protocol
• Redacted Statistical Analysis Plan
• Redacted CSR synopsis

MeSH Terms

Conditions

Neurofibromatosis 1; Neurofibroma, Plexiform

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Alice P. Chen, MD

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: June 14, 2021
• Study Start: November 19, 2021
• Primary Completion: August 5, 2024
• Study Completion (Estimated): February 15, 2029
• Last Updated: March 23, 2026
• Results First Posted: October 20, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

FR (3); RU (2); JP (3); AU (2); BR (3); CA (2); CN (4); ES (2); GB (2); US (4); IT (3); PL (1); DE (3)