Actively Recruiting
Multi-Center Phase I Study of Avutometinib (VS-6766), a RAF/MEK Clamp, with Defactinib, a FAK Inhibitor, in Pediatric Patients with Refractory or Recurrent Solid Tumors Harboring MAPK Pathway or NF2 Alterations
Led by Memorial Sloan Kettering Cancer Center · Updated on 2026-02-25
23
Participants Needed
2
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety of avutometinib as a treatment for children and young adults aged 3 to 30 years with advanced or recurrent solid tumor cancers, including pediatric tumors with specific genetic alterations affecting the MAP kinase pathway and certain neurofibromatosis conditions. This phase 1 study aims to find the highest dose of avutometinib that is safe and causes few or mild side effects. Participants receive oral avutometinib twice a week, once daily, in cycles of three weeks on treatment followed by one week off, with each cycle lasting 28 days. The study uses a dose-escalation design, starting at Dose Level 1 and adjusting the dose based on the number of dose-limiting toxicities (DLTs) observed, to identify the maximum tolerated dose (MTD). During the study, participants will be closely monitored for safety over up to 12 months. Researchers will assess side effects and tolerability, and participants will undergo regular evaluations including clinical assessments and laboratory tests. The study carefully tracks adverse events and adjusts dosing to ensure participant safety throughout the trial.
CONDITIONS
Brief Title
A Study of Avutometinib for People With Solid Tumor Cancers
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 3 and 30 years at the time of consent
- Written informed consent signed by patient or legal representative; assent as appropriate
- Karnofsky score ≥ 50% for patients > 16 years; Lansky score ≥ 50 for patients ≤ 16 years
- Diagnosis of pediatric tumor with activating MAP kinase pathway alterations or NF1 with symptomatic inoperable plexiform neurofibromas or recurrent optic pathway gliomas with clinical progression
- Genetic confirmation of NF2 schwannomatosis with documented tumor progression
- Measurable or evaluable disease as defined by RECIST or MRI criteria depending on tumor type
- Tumor refractory or recurrent after at least one prior standard therapy unless no adequate options exist
- Body surface area ≥ 0.8 m2
- Ability to swallow intact capsules
- May have prior monotherapy with RAF or MEK inhibitors
- Fully recovered from prior anti-cancer therapy with specified waiting periods
- Adequate liver, kidney, and blood function within defined limits
- Males and females of reproductive potential must agree to use effective birth control during study and for specified times after last dose
You will not qualify if you...
- History of rhabdomyolysis
- History of glaucoma, retinal vein occlusion, or significant ocular disorders increasing risk for retinal vein occlusion
- History of corneal erosion, degeneration, keratitis, or other serious inflammatory eye conditions
- Hypersensitivity to inactive ingredients of the study drug
- Active diarrhea requiring medication within 7 days
- Significant cardiac disease or risk factors including congestive heart failure or low heart function
- QTc interval > 470 msec, history of Torsades de Pointes, or congenital long QT syndrome
- Active hepatitis B, hepatitis C, or HIV infection requiring therapy
- Use of strong CYP3A4 inhibitors or inducers within 14 days prior to first dose and during treatment
- Pregnant or breastfeeding women are excluded
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Repeated 28-day cycles until disease progression or discontinuation
Participants receive oral avutometinib once daily twice a week, three weeks on followed by one week off, for cycles of 28 days each.
Weekly visits for treatment assessments
Trial Site Locations
Total: 2 locations
1
Children's Healthcare of Atlanta (Data Collection Only)
Atlanta, Georgia, United States, 30322
Actively Recruiting
2
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, United States, 10065
Actively Recruiting
Research Team
S
Sameer Farouk Sait, MD
J
Julia Glade Bender, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
3
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