MPNST (Malignant Peripheral Nerve Sheath Tumor)Phase 2NF120NCT07743554
Combination of Avutometinib and Defactinib for Treatment of Relapsed, Refractory, Metastatic, or Unresectable Malignant Peripheral Nerve Sheath Tumor
A Phase 2 study testing avutometinib capsule + defactinib tablet in people with MPNST (Malignant Peripheral Nerve Sheath Tumor), run by Girish Dhall, MD.
Trial summary
The purpose of this study is to learn whether the study drugs avutometinib and defactinib can help stop or shrink malignant peripheral nerve sheath tumors (MPNST) that have returned or cannot be removed with surgery. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- MPNST (Malignant Peripheral Nerve Sheath Tumor)
- What is being tested?
- avutometinib capsule + defactinib tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2027to Jan 2032
- Phase
- Phase 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age > 12 years old with a body surface area (BSA) of at least 1.5 mm2
- DIAGNOSIS: Participants with relapsed, refractory, unresectable or metastatic histologically confirmed NF1 associated or sporadic MPNST.
- Participants must have available archival tissue. Tissue blocks strongly preferred. Exceptions may be made following discussion with study team if tissue has been exhausted.
- MEASURABLE DISEASE: Participants must have measurable disease by RECIST v1.1.
- THERAPEUTIC OPTIONS: Participants must have experienced relapse/progression or demonstrated disease that is refractory to one or more prior regimens of cytotoxic chemotherapy or participants who must have declined cytotoxic chemotherapy.
- PRIOR THERAPY
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- Participants may not have previous exposure to combination treatment with a MEK/FAK inhibitor in combination. Participants may have received MEK inhibitor or FAK inhibitor as a single agent for prior therapy.
- Participants must have not had a serious adverse event (CTCAE grade III or IV) to prior MEK inhibitor or FAK inhibitor drugs.
- Participants must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering on this study. If the participant is experiencing unresolved toxicity from previous treatment they may still be enrolled in the study as long as it is not expected to be worsened by active treatment or deemed unsafe by the study team.
- No limitation on the number of prior chemotherapy regimens the participant may have received before study entry.
- Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancer drugs must be at least 2 weeks before study entry as long as hematologic parameters have returned to the minimum study requirements.
- Immunotherapy: The last dose of immunotherapy (monoclonal antibody or vaccine) must be at least 4 weeks before study entry. Cellular therapies: At least 6-week washout from immune cell engaging bispecific antibodies, genetically modified T cell, NK cell, or dendritic cell therapy.
- Biologic (anti-cancer agent): The last dose of all biologic agents for the treatment of the participant's cancer (such as retinoids or tyrosine kinase inhibitors) must be at least 14 days prior to study entry.
- Radiation therapy: The last dose of radiation to more than 25% of marrow-containing bones (pelvis, spine, skull) must be at least 4 weeks before study entry. The last dose of all other local palliative (limited port) radiation must be at least 2 weeks before 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.
- Investigational agents: At least a 4-week washout from other investigational agents.
- Interleukins, interferons, and cytokine therapy: At least 3 weeks washout period from the last administered Interleukins, interferons, and cytokine therapy other than hematopoietic growth factors
- 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) is permitted while on trial with this regimen.
- PERFORMANCE STATUS
- Lansky/Karnofsky performance level ≥ 50% (Appendix 4).
- Participants who are unable to walk because of paralysis or motor weakness, but who are up in a wheelchair will be considered ambulatory for the purpose of calculating the performance score.
- HEMATOLOGIC FUNCTION
- Peripheral absolute neutrophil count (ANC) of ≥1000/μL
- Platelet count ≥75,000/μL.
- Hemoglobin >8 g/dL (transfusion permissible).
- HEPATIC FUNCTION
- Total bilirubin must be ≤ 1.5 times the upper limit of normal (ULN) (for participants with Gilbert's disease ≤3x ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN (or < 5 x ULN in participants with liver metastases).
- RENAL FUNCTION: Serum creatinine ≤ ULN or creatinine clearance >30 ml/min/1.73 m2
- Serum triglyceride level ≤300 mg/dL and serum cholesterol level ≤ 300 mg/dL (Participant may be on lipid-lowering medicine)
- International normalized ratio (INR) <1.5
- Albumin > 3 g/dL (451 μmol/L)
- Creatine phosphokinase (CPK) < 2.5 x ULN
- CARDIAC FUNCTION:
- Normal ejection fraction by echocardiogram, cardiac MRI >50%, or institutional standard
- QTcF ≤ 480ms
- Fertile men and women of childbearing potential must agree to use an effective method of birth control.
- Participants 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
- Current warfarin use. If a participant is currently being treated for a pulmonary embolism with warfarin, they may be eligible if they are able to be converted to a Direct Oral Anticoagulant (DOAC) or low molecular weight heparin.
- History of another active malignancy. Prior malignancy, that has been curatively treated or malignancies with very low potential for recurrence or progression may be included.
- Major surgery within 4 weeks (excluding placement of vascular access, or core needle biopsy), minor surgery within 2 weeks.
- Exposure to medications (with or without prescription), supplements, herbal remedies, or foods with potential for drug-drug interactions with avutometinib and/or defactinib within 5 half-lives (if known), or 14 days prior to the first dose of study intervention, whichever is longer.
- Symptomatic brain metastases requiring steroids above the physiologic dose for adrenal insufficiency or other local interventions. Participants with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment (greater than physiologic dosing) for these metastases for at least 2 weeks prior to first dose of study therapy, and are neurologically stable, with no evidence of interim progression. Participants with new asymptomatic CNS metastases detected during the screening period must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these participants may then be eligible if all other criteria are met.
- Known hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection that is active and/or requires therapy.
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- Uncontrolled skin disorders (i.e. psoriasis, lupus dermatitis, rosacea) that may confound the interpretation of the safety findings from the study treatments. If the skin condition is adequately controlled and the participant is on a stable dose of controlling medications, they may be eligible for this study.
- History of medically significant rhabdomyolysis.
- Concurrent ocular disorders:
- Baseline best corrected visual acuity of 20/80 or worse.
- Participants with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes.
- Participants with history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, intraocular pressure > 21 mm Hg as measured by tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO.
- Participants with active or chronic, visually significant corneal disorders, other active ocular conditions requiring ongoing therapy or clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy. Examples of visually significant corneal disorders include corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions. Visually significant corneal disorders do NOT include dry eyes, blepharitis, and uncomplicated corneal erosions.
- Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), myocardial infarction within the last 6 months, unstable arrhythmias, unstable angina, severe obstructive pulmonary disease, or persistent, uncontrolled hypertension defined as systolic blood pressure >140 mmHg or diastolic blood pressure> 90mmHg. Participants may qualify if their blood pressure is controlled on anti-hypertensive agents.
- Participants with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease.
- Participants with a history of hypersensitivity to any of the active or inactive avutometinib and/or defactinib ingredients (hydroxypropylmethylcellulose, mannitol, magnesium stearate).
- Female subjects who are pregnant or breastfeeding.
- Any other medical condition (e.g., cardiac, gastrointestinal, pulmonary, psychiatric, neurological, genetic, etc.) that in the opinion of the investigator would place the participant at unacceptably high risk for toxicity.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
The purpose of this study is to learn whether the study drugs avutometinib and defactinib can help stop or shrink malignant peripheral nerve sheath tumors (MPNST) that have returned or cannot be removed with surgery.
Read the detailed description
This is a phase 2 study for 12 year olds and older to learn about the safety, side effects, and how well the study drugs, avutometinib and defactinib, work when used together in people with MPNST that has spread to other parts of the body (metastatic) or cannot be removed with surgery (unresectable) and has continued to grow or gotten worse after chemotherapy.
- Being tested
- avutometinib capsule + defactinib tablet
- Keywords
- MPNST, metastatic, unresectable, NF1, Neurofibromatosis Type 1
- Medical subject headings
- Neurofibrosarcoma, Neoplasm Metastasis, Neurofibromatosis 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
avutometinib capsule + defactinib tabletDrug
avutometinib in combination with defactinib in participants with metastatic or unresectable MPNST
| Study group | Role | What they receive |
|---|---|---|
| Phase 2 defactinib and avutometinib combination | Experimental | Avutometinib will be given at 3.2 mg (4 x 0.8 mg capsule) twice a week. One cycle of treatment consists of three weeks of treatment and one week off treatment.
Defactinib will be given at 200 mg (1 x 200 mg tablet) twice a day. One cycle of treatment consists of three weeks of treatment and one week off treatment. Receives: Drug: avutometinib capsule + defactinib tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of participants that were progression free at four months treated with defactinib and avutometinib.
The primary endpoint will be progression free survival (PFS) at four months. PFS is defined as time from initiation of therapy to progression (per RECIST v1.1) or death due to any causes. The primary endpoint is PFS at 4 months, evaluated 15-18 weeks from the initiation of therapy.
Measured: 4 months
Secondary outcomes (2)
To define and describe the toxicities of the combination therapy with defactinib and avutometinib
Adverse events based on the NCI Common Terminology Criteria (CTC) version 5.0
Measured: up to 25 months
To estimate tumor objective response rate
Objective response rate will be defined as Complete response (CR), partial response (PR), at 4 months will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2026
- Study start1 Jan 2027 (estimated)
- Primary completionJan 2031 (estimated)
- Study completionJan 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MPNST (Malignant Peripheral Nerve Sheath Tumor)Studies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Girish Dhall, MD
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense, Children's Hospital of Philadelphia, Washington University School of Medicine
- Responsible party
- Sponsor-investigator, Girish Dhall, MD, University of Alabama at Birmingham
- Investigators
- Girish Dhall, MD, Study director, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07743554
- Sponsor's protocol ID
- STUDY00000350
- Other IDs
- AWD00000465, UFA00000062
- Acronym
- NF120
- Status last verified
- Jul 2026
- First submitted
- 30 Jul 2026
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data obtained through this study may be provided to qualified researchers with academic interest in NF1, NF2 and schwannomatosis. Data shared will be coded, with no PHI included. Approval of the request and execution of all applicable agreements (i.e. a material/data transfer agreement) are prerequisites to the sharing of data with the requesting party. Data requests can be made to the NFCTC following publication of the article describing trial results. Requests that conflict with ongoing or future planned analyses may be denied. All data requests must be reviewed and approved by the NFCTC.
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination of Avutometinib and Defactinib for Treatment of Relapsed, Refractory, Metastatic, or Unresectable Malignant Peripheral Nerve Sheath Tumor
- ClinicalTrials.gov ID
- NCT07743554
- Acronym / sponsor ID
- NF120 / STUDY00000350
- Keywords
- MPNST, metastatic, unresectable, NF1, Neurofibromatosis Type 1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Girish Dhall, MDUniversity, hospital or other
- Collaborators
- United States Department of Defense, Children's Hospital of Philadelphia, Washington University School of Medicine
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- Jan 2031 (estimated)
- Study completion
- Jan 2032 (estimated)
- First posted
- 4 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to learn whether the study drugs avutometinib and defactinib can help stop or shrink malignant peripheral nerve sheath tumors (MPNST) that have returned or cannot be removed with surgery.
Detailed description
This is a phase 2 study for 12 year olds and older to learn about the safety, side effects, and how well the study drugs, avutometinib and defactinib, work when used together in people with MPNST that has spread to other parts of the body (metastatic) or cannot be removed with surgery (unresectable) and has continued to grow or gotten worse after chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase 2 defactinib and avutometinib combination | Experimental | Drug: avutometinib capsule + defactinib tabletAvutometinib will be given at 3.2 mg (4 x 0.8 mg capsule) twice a week. One cycle of treatment consists of three weeks of treatment and one week off treatment. Defactinib will be given at 200 mg (1 x 200 mg tablet) twice a day. One cycle of treatment consists of three weeks of treatment and one week off treatment. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (39 listed)
- Age > 12 years old with a body surface area (BSA) of at least 1.5 mm2
- DIAGNOSIS: Participants with relapsed, refractory, unresectable or metastatic histologically confirmed NF1 associated or sporadic MPNST.
- Participants must have available archival tissue. Tissue blocks strongly preferred. Exceptions may be made following discussion with study team if tissue has been exhausted.
- MEASURABLE DISEASE: Participants must have measurable disease by RECIST v1.1.
- THERAPEUTIC OPTIONS: Participants must have experienced relapse/progression or demonstrated disease that is refractory to one or more prior regimens of cytotoxic chemotherapy or participants who must have declined cytotoxic chemotherapy.
Key exclusion criteria (18 listed)
- Current warfarin use. If a participant is currently being treated for a pulmonary embolism with warfarin, they may be eligible if they are able to be converted to a Direct Oral Anticoagulant (DOAC) or low molecular weight heparin.
- History of another active malignancy. Prior malignancy, that has been curatively treated or malignancies with very low potential for recurrence or progression may be included.
- Major surgery within 4 weeks (excluding placement of vascular access, or core needle biopsy), minor surgery within 2 weeks.
- Exposure to medications (with or without prescription), supplements, herbal remedies, or foods with potential for drug-drug interactions with avutometinib and/or defactinib within 5 half-lives (if known), or 14 days prior to the first dose of study intervention, whichever is longer.
- Symptomatic brain metastases requiring steroids above the physiologic dose for adrenal insufficiency or other local interventions. Participants with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment (greater than physiologic dosing) for these metastases for at least 2 weeks prior to first dose of study therapy, and are neurologically stable, with no evidence of interim progression. Participants with new asymptomatic CNS metastases detected during the screening period must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these participants may then be eligible if all other criteria are met.
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 |
|---|---|---|
| avutometinib capsule + defactinib tabletavutometinib in combination with defactinib in participants with metastatic or unresectable MPNST | Drug | Phase 2 defactinib and avutometinib combination |
Primary outcome
The number of participants that were progression free at four months treated with defactinib and avutometinib.
Time frame: 4 months
The primary endpoint will be progression free survival (PFS) at four months. PFS is defined as time from initiation of therapy to progression (per RECIST v1.1) or death due to any causes. The primary endpoint is PFS at 4 months, evaluated 15-18 weeks from the initiation of therapy.
2 secondary outcomes
To define and describe the toxicities of the combination therapy with defactinib and avutometinib
Time frame: up to 25 months
To estimate tumor objective response rate
Time frame: 4 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Individual participant dataSharing planned: Yes. Data obtained through this study may be provided to qualified researchers with academic interest in NF1, NF2 and schwannomatosis. Data shared will be coded, with no PHI included. Approval of the request and execution of all applicable agreements (i.e. a material/data transfer agreement) are prerequisites to the sharing of data with the requesting party. Data requests can be made to the NFCTC following publication of the article describing trial results. Requests that conflict with ongoing or future planned analyses may be denied. All data requests must be reviewed and approved by the NFCTC.
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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.
Girish Dhall, MD study director
University of Alabama at Birmingham
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing avutometinib capsule + defactinib tablet in people with MPNST (Malignant Peripheral Nerve Sheath Tumor), run by Girish Dhall, MD.
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 39 inclusion and 18 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: opening soon, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
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 Juliette Southworth, BS, CCRP (12055298967, jsouthworth@uab.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of participants that were progression free at four months treated with defactinib and avutometinib. (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Oct 2026.