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Malignant Peripheral Nerve Sheath Tumor (MPNST)Phase 1/2MEKMDM2NCT06735820

Early Phase Study Evaluating MEK and MDM2 Inhibition in Patients With NF1 and MPNST

A Phase 1/2 study testing APG-115 and Selumetinib in people with Malignant Peripheral Nerve Sheath Tumor (MPNST) and Neurofibromatosis 1 (NF1), run by AeRang Kim at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is a phase 0/1/2, multi-site study to evaluate the MEK inhibitor Selumetinib with the MDM2 Inhibitor APG-115 in patients with Neurofibromatosis Type 1 and pre-malignant and malignant peripheral nerve sheath tumors Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
APG-115 and Selumetinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
2 sitesUnited States
Study dates
1 Jun 2026to 1 Oct 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • AGE: Part A and C: ≥ 18 years of age AGE: Part B: ≥12 years (minimum BSA ≥0.55m2)
  • Part A and B: Patients with unresectable or metastatic histologically confirmed NF1 associated MPNST. Part C: Patients with NF1 and ANNUBP. Diagnostic criteria based on Miettinen et al, Human Pathol:
  • MEASURABLE DISEASE: Patients must have measurable disease by RECISTv1.1. Baseline radiologic scans must be performed within 4 weeks of starting treatment.
  • Therapeutic options: Parts A and B: Patients must have experienced progression after one or more prior regimens of cytotoxic chemotherapy. Patients who have refused cytotoxic chemotherapy or for whom treatment on this protocol prior to receiving cytotoxic chemotherapy is felt to be in the best interest for the patient by the local investigator will also be eligible. Part C: Patients with ANNUBP that are planned for surgical resection
  • PRIOR THERAPY
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering on this study excluding chronic grade 1 toxicities and alopecia.
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  • No limitation on the number of prior chemotherapy regimens that the patient may have received prior to study entry.
  • Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancer drugs must be at least 3 weeks (≥21 days) prior to study entry (42 days if prior nitrosourea).
  • Immunotherapy: The last dose of immunotherapy (monoclonal antibody or vaccine) must be at least 4 weeks prior to study entry.
  • Anti-cancer agents not known to be myelosuppressive (e.g not associated with reduced platelets or ANC count): ≥7 days after the last dose of the agent .
  • Radiation therapy: The last dose of radiation to more than 25% of marrow containing bones (pelvis, spine, skull) must be at least 4 weeks prior to study entry. The last dose of all other local palliative (limited port) radiation must be at least 2 weeks prior to study entry.
  • Stem Cell Transplantation. At least 2 months post-autologous stem cell transplant or at least 3 months post-allogeneic transplant and recovered from toxicities without evidence of graft versus host disease and on stable doses of immunosuppressive medications, if required.
  • Growth Factors. The last dose of colony stimulating factors, such as filgrastim, sargramostim, and erythropoietin, must be at least 1 week prior to study entry, the last dose of long-acting colony stimulating factors, such as pegfilgrastim, must be at least 2 weeks prior to study entry.
  • Concurrent therapies: No other anti-cancer therapy (chemotherapy, biological therapy, radiation therapy) permitted.
  • PERFORMANCE STATUS
  • Lansky/Karnofsky performance level ≥ 50% . Participants who are wheelchair bound or have limited mobility secondary to a need for mechanical breathing support (such as an airway PN requiring tracheostomy or continuous positive airway pressure) who must have a Lansky performance of ≥ 40 (Appendix related to performance status scale).
  • For patients ≥18: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
  • Patients who are unable to walk because of paralysis or motor weakness, but who are able to use a wheelchair will be considered ambulatory for the purpose of calculating the performance score.
  • HEMATOLOGIC FUNCTION
  • Hemoglobin ≥9.0 g/dL (transfusion permissible)
  • Peripheral absolute neutrophil count (ANC) of ≥1000/μL
  • Platelet count ≥75,000/μL (transfusion independent (no transfusion within at least 7 days prior to enrollment))
  • HEPATIC FUNCTION
  • Total bilirubin must be ≤ 1.5 times the upper limit of normal (ULN) or ≤3×ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia).
  • SGOT (AST)/SGPT (ALT) must be ≤ 3.0 times ULN
  • RENAL FUNCTION: Serum creatinine ≤ 1.5 times ULN or creatinine clearance >60 ml/min/1.73m2
  • CARDIAC FUNCTION:
  • Normal ejection fraction by ECHO by institutional normal (within 4 weeks of enrollment)
  • QTc ≤ 450msec (within 4 weeks of enrollment)
  • Fertile men and women of childbearing potential must agree to use an effective method of birth control.
  • CNS DISEASE: Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease and are without evidence of clinical progression or stable disease at 4 weeks.

Who cannot join

  • History of another primary malignancy except for:
  • A malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of the study intervention and of low potential risk of recurrence.
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
  • Stable optic pathway glioma or low-grade glioma not receiving active therapy
  • History of leptomeningeal carcinomatosis
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  • Patients receiving other anti-cancer agents are not eligible.
  • Patients who cannot swallow whole pills.
  • Current or prior use of immunosuppressive medications within 14 days prior to study entry. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids or local steroid injection (e.g., intra-articular injection)
  • Systemic corticosteroids used at physiologic doses not to exceed 10mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Any recent major surgery within a minimum of 4 weeks prior to starting drug therapy. Placement of vascular access device, percutaneous tumor biopsy, or bone marrows are not considered major surgical procedures and no minimum time frame prior to starting study drug therapy is required.
  • Patients who have any known severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
  • Severely impaired lung function defined as spirometry and DLCO that is 50% of the normal predicted value corrected for hemoglobin and alveolar volume and/or O2 saturation that is 88% or less at rest on room air. For patients who do NOT have respiratory symptoms (e.g., dyspnea at rest, known requirement for supplemental oxygen), pulmonary function test is not required.
  • Cardiac conditions as follows:
  • Uncontrolled hypertension (blood pressure ≥≥140/90 mmHg despite medical therapy.
  • For pediatric patients: blood pressure ≥95th percentile for age, height, and gender measured as described in Appendix VIII
  • Known inherited coronary disease;
  • For studies with pediatric patients: History of angina or acute coronary syndrome; Acute coronary syndrome within 6 months prior to starting drug therapy
  • Uncontrolled angina despite medical therapy (Canadian Cardiovascular Society grade II-IV despite medical therapy (Appendix IV))
  • Symptomatic heart failure NYHA Class II-IV prior or current cardiomyopathy or severe valvular disease (Appendix V)
  • Prior or current cardiomyopathy including but not limited to the following
  • Known hypertrophic cardiomyopathy
  • Known arrhythmogenic right ventricular cardiomyopathy
  • Previous moderate or severe impairment of left ventricular systolic function (LVEF <45% on echocardiography or equivalent of MUGA) even if full recovery has occurred
  • Symptomatic or uncontrolled atrial fibrillation despite treatment or asymptomatic sustained ventricular tachycardia.
  • Active primary immunodeficiency
  • Ophthalmological conditions as follows (ophthalmology exam within 4 weeks of study enrollment)
  • Current or past history of retinal pigment epithelial detachment/central serous retinopathy or retinal vein occlusion
  • Known intraocular pressure (IOP)>21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma.
  • Any other significant abnormality on ophthalmic examination that would make the subject unsuitable for enrolment into the study, as assessed by the investigator.
  • Subjects with ophthalmological findings secondary to long standing optic pathway glioma (such as visual loss, optic nerve pallor, or strabismus) or long standing orbito-temporal PN (such as vision loss, strabismus) will not be considered a significant abnormality for purposes of this study.
  • Any Supplementation with vitamin E in the 7 days prior to initiation of selumetinib.
  • Hypersensitivity to investigational products, or drugs with similar chemical structures to investigational products.
  • Patients unwilling or unable to comply with the protocol.
  • Seville orange, star fruit, grapefruit juice, St. Johns' Wort use are not allowed while on study.
  • Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of selumetinib.
  • Receiving herbal supplements or medications known to be strong or moderate inhibitors or inducers of the cytochrome P450 (CYP)2C19 and CYP3A4 enzymes or fluconazole unless such products can be safely discontinued at least 14 days or 5 half-lives (whichever is longer) before the first dose of study medication.
  • Persistent toxicities (CTCAE Grade ≥2) caused by previous anticancer therapy, excluding hair changes such as alopecia or hair lightening.
  • Currently pregnant (confirmed with positive pregnancy test) or breastfeeding (lactation must be discontinued throughout the period of the study and until at least one week after the last dose of study intervention)

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Vidya Chenji contact

202-476-3745

nchenji@childrensnational.org

United States2 sites, 2 recruiting

  • UT Southwestern Medical Center

    Dallas, Texas, 75235

    Parker Straight, 214-456-0311, Parker.Straight@childrens.com

    Ivan Sy, 214-456-0311, Ivan.Sy@childrens.com

    Recruiting

  • Children's National Hospital

    Washington D.C., District of Columbia, 20010

    Recruiting

Other trials in United States

About this study

Official title: Early Phase Study to Evaluate the MEK Inhibitor Selumetinib With the MDM2 Inhibitor APG-115 in Patients With Neurofibromatosis Type 1 and Pre-malignant and Malignant Peripheral Nerve Sheath Tumors

This is a phase 0/1/2, multi-site study to evaluate the MEK inhibitor Selumetinib with the MDM2 Inhibitor APG-115 in patients with Neurofibromatosis Type 1 and pre-malignant and malignant peripheral nerve sheath tumors

Read the detailed description

The first primary objective of the study is to determine the safety, tolerability, pharmacokinetics, and recommended doses of selumetinib and APG-115 in patients with Neurofibromatosis Type 1 (NF1) and refractory/unresectable MPNST (Part A). The second primary objective is to determine the clinical benefit of selumetinib and APG-115 in patients with NF1 and refractory/unresectable MPNST (Part B). The secondary objective is to evaluate the percent apoptosis and tumor proliferation in resectable atypical neurofibromatus neoplasm of uncertain biologic potential (ANNUBP) after exposure to selumetinib and APG-115 (Part C)

Being tested
APG-115, Selumetinib
Keywords
NF1, MPNST, MEK inhibitor, MDM2 inhibitor, atypical neurofibroma, ANNUBP
Medical subject headings
Neurofibrosarcoma, Neurofibromatosis 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APG-115Drug

    Also called alrizomadlin

    Combination therapy of APG-115 and Selumetinib

  • SelumetinibDrug

    Also called koselugo

    Combination therapy of APG-115 and Selumetinib

Study groups in NCT06735820
Study groupRoleWhat they receive
APG-115 and SelumetinibExperimentalThere is only one arm. It is combination therapy of APG-115 and Selumetinib.
Receives: Drug: APG-115; Drug: Selumetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The number of treated patients with adverse events as determined by the common criteria for adverse version 5 (CTCAEv5).

    We will be looking at safety and dose recommendations using adverse event evaluation per dose level as determined by CTCAEv5 (Part A)

    Measured: 15 months

  2. Tumor response by imaging using RECISTv1.1

    We will determine the clinical benefit of this combination by evaluating tumor response by imaging using RECISTv1.1 guidelines (Part B)

    Measured: 28 months

Secondary outcomes (1)

  1. Percent apoptosis and tumor proliferation

    To evaluate the percent apoptosis and tumor proliferation in resected tumor tissue ANNUBP after exposure to selumetinib and APG-115 (Part C)

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2024
  2. Study start1 Jun 2026
  3. Primary completion1 Oct 2027 (estimated)
  4. Study completion1 Oct 2028 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
45 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06735820
Sponsor's protocol ID
STUDY00001200
Other IDs
W81XWH-22-1-1120
Acronym
MEKMDM2
Status last verified
Jul 2026
First submitted
9 Dec 2024
Last updated
27 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing APG-115 and Selumetinib in people with Malignant Peripheral Nerve Sheath Tumor (MPNST) and Neurofibromatosis 1 (NF1), run by AeRang Kim at 2 sites in United States.

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 31 inclusion and 41 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: looking for participants now, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Vidya Chenji (202-476-3745, nchenji@childrensnational.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The number of treated patients with adverse events as determined by the common criteria for adverse version 5 (CTCAEv5). (time frame: 15 months). The study lists 2 primary outcomes in all. 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 NCT06735820.

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 27 Jul 2026.

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