Neurofibromatosis 1Phase 3KOMETNCT04924608
Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas
A Phase 3 study testing Selumetinib in people with Neurofibromatosis 1 and Plexiform Neurofibroma (PN), run by AstraZeneca at 34 sites in 13 countries.
Trial summary
A global study to demonstrate the effectiveness of selumetinib in participants with NF1 who have symptomatic, inoperable plexiform neurofibromas. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurofibromatosis 1, Plexiform Neurofibroma (PN)
- What is being tested?
- Selumetinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 145 participants
- Where
- 34 sitesin 13 countries
- Study dates
- 19 Nov 2021to 15 Feb 2029
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Confirmed or suspected malignant glioma or MPNST (low grade glioma, including optic glioma not requiring systemic therapy or radiation therapy are exempt from this exclusion)
- 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
Trial locations and contacts
34 sites in 13 countries.
34 sites in 13 countries
United States4 sites
Research Site
Commack, New York, 11725
Research Site
Gainesville, Florida, 32610
Research Site
Rockville, Maryland, 20852
Research Site
St Louis, Missouri, 63156
China4 sites
Research Site
Beijing, 100070
Research Site
Beijing, 100730
Research Site
Guangzhou, 510060
Research Site
Shenyang, 110001
Brazil3 sites
Research Site
Porto Alegre, 90035-903
Research Site
Ribeirão Preto, 14051-140
Research Site
São Paulo, 045202-001
France3 sites
Research Site
Créteil, 94000
Research Site
Lyon, 69008
Research Site
Toulouse, 31059
Germany3 sites
Research Site
Hamburg, 20246
Research Site
Tübingen, 72076
Research Site
Würzburg, 97080
Italy3 sites
Research Site
Milan, 20133
Research Site
Naples, 80131
Research Site
Roma, 00165
Japan3 sites
Research Site
Minatoku, 105-8471
Research Site
Nagoya, 466-8560
Research Site
Shinjuku-ku, 160-8582
Australia2 sites
Research Site
Melbourne, 3000
Research Site
St Leonards, 2065
Canada2 sites
Research Site
Montreal, Quebec, H4A 3J1
Research Site
Toronto, Ontario, M5G 2C4
United Kingdom2 sites
Research Site
London, SE1 9RT
Research Site
Manchester, M20 4BX
About this study
Official title: A Phase III, Multicentre, International Study With a Parallel, Randomised, Double-blind, Placebo-controlled, 2 Arm Design to Assess the Efficacy and Safety of Selumetinib in Adult Participants With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas (KOMET)
A global study to demonstrate the effectiveness of selumetinib in participants with NF1 who have symptomatic, inoperable plexiform neurofibromas.
Read the detailed description
This is a randomized, double-blind, placebo-controlled, 2 arm multicentre, global Phase III study to assess the efficacy and safety of selumetinib compared with placebo in adult participants with NF1 who have symptomatic, inoperable PN.
- Conditions
- Neurofibromatosis 1, Plexiform Neurofibroma (PN)
- Being tested
- Selumetinib, Placebo
- Keywords
- Neurofibromatosis Type 1, NF1, Plexiform Neurofibroma (PN), PNs, Selumetinib, MEK inhibitor
- Medical subject headings
- Neurofibromatosis 1, Neurofibroma, Plexiform
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelumetinibDrug
Also called AZD6244
Selumetinib oral capsules (10 mg and 25 mg)
PlaceboOther
Placebo oral capsules for Selumetinib masking (10 mg and 25 mg)
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Selumetinib Receives: Drug: Selumetinib |
| Arm B | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The PAINS-pNF (Pain Intensity Scale for Plexiform Neurofibroma) chronic target PN pain intensity measures the participants' experience of chronic PN-related pain intensity with score from 0 (no chronic tumor pain) to 10 (worst chronic tumor pain). Baseline PAINS-pNF chronic target PN pain score is defined as the average of the available daily PAINS-pNF chronic target PN pain scores in the screening perio, while for Cycle 12, it is defined as the average of the available daily scores for the 28-days cycle up to and including the last day assessment of cycle 12. The difference of the means in the change from baseline at Cycle 12 between selumetinib and placebo in participants with a PAINS-pNF chronic target PN pain score of ≥ 3 at baseline is presented.
Measured: 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
The PAINS-pNF (Pain Intensity Scale for Plexiform Neurofibroma) chronic target PN pain intensity measures the participants' experience of chronic PN-related pain intensity with score from 0 (no chronic tumor pain) to 10 (worst chronic tumor pain). Baseline PAINS-pNF chronic target PN pain score is defined as the average of the available daily PAINS-pNF chronic target PN pain scores in the screening perio, while for Cycle 12, it is defined as the average of the available daily scores for the 28-days cycle up to and including the last day assessment of cycle 12. The difference of the means in the change from baseline at Cycle 12 between selumetinib and placebo participants is presented.
Measured: 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
PlexiQoL (Plexiform Neurofibroma Quality of Life scale) is a patient-derived QoL measure specific to adults with NF1-associated PNs. It assesses the impact of PNs on patients' ability to fulfil their human needs. The measure consists of 18 dichotomous items with 0 =Not True and 1 = True. PlexiQoL total scores were calculated by the sum of all items to a maximum of 18, with lower scores indicating better quality of life. The change from baseline to the end of each cycle in PlexiQoL total score was derived as the PlexiQoL total score at the cycle 12 minus baseline PlexiQoL total score and presented.
Measured: Baseline and end of Cycle 12 of study intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2021
- Study start19 Nov 2021
- Primary completion5 Aug 2024
- Study completion15 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neurofibromatosis 1Studies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 145 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Alice P. Chen, MD, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04924608
- Sponsor's protocol ID
- D134BC00001
- Other IDs
- 2020-005607-39
- Acronym
- KOMET
- Status last verified
- Mar 2026
- First submitted
- 14 May 2021
- Last updated
- 23 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Publications
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.
PubMed 40473450
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Multicentre, International Study With a Parallel, Randomised, Double-blind, Placebo-controlled, 2 Arm Design to Assess the Efficacy and Safety of Selumetinib in Adult Participants With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas (KOMET)
- ClinicalTrials.gov ID
- NCT04924608
- Acronym / sponsor ID
- KOMET / D134BC00001
- Conditions
- Neurofibromatosis 1, Plexiform Neurofibroma (PN)
- Keywords
- Neurofibromatosis Type 1, NF1, Plexiform Neurofibroma (PN), PNs, Selumetinib, MEK inhibitor
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 145 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 19 Nov 2021 (actual)
- Primary completion
- 5 Aug 2024 (actual)
- Study completion
- 15 Feb 2029 (estimated)
- First posted
- 14 Jun 2021 (actual)
- Results
- Posted 20 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A global study to demonstrate the effectiveness of selumetinib in participants with NF1 who have symptomatic, inoperable plexiform neurofibromas.
Detailed description
This is a randomized, double-blind, placebo-controlled, 2 arm multicentre, global Phase III study to assess the efficacy and safety of selumetinib compared with placebo in adult participants with NF1 who have symptomatic, inoperable PN.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: SelumetinibSelumetinib |
| Arm B | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- Confirmed or suspected malignant glioma or MPNST (low grade glioma, including optic glioma not requiring systemic therapy or radiation therapy are exempt from this exclusion)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SelumetinibAlso: AZD6244Selumetinib oral capsules (10 mg and 25 mg) | Drug | Arm A |
| PlaceboPlacebo oral capsules for Selumetinib masking (10 mg and 25 mg) | Other | Arm B |
Primary outcome
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.
Time frame: 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)
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.
3 secondary outcomes
(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
Time frame: 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
Time frame: 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
Time frame: Baseline and end of Cycle 12 of study intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40473450Chen 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.
- Redacted ProtocolLink provided by the sponsor.
- Redacted Statistical Analysis PlanLink provided by the sponsor.
- Redacted CSR synopsisLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alice P. Chen, MD principal investigator
National Cancer Institute (NCI)
34 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Selumetinib in people with Neurofibromatosis 1 and Plexiform Neurofibroma (PN), run by AstraZeneca at 34 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 23 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in United States, China, Brazil, France, Germany and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04924608, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2026.