Actively Recruiting
Defactinib and Avutometinib, With or Without Encorafenib, for the Treatment of Patients With Brain Metastases From Cutaneous Melanoma
Led by University of Utah · Updated on 2025-12-03
33
Participants Needed
2
Research Sites
303 weeks
Total Duration
On this page
Sponsors
U
University of Utah
Lead Sponsor
V
Verastem, Inc.
Collaborating Sponsor
AI-Summary
What this Trial Is About
The goal of this interventional clinical trial is to provide proof-of-principle data for the biologic activity of defactinib in combination with avutometinib in brain metastases from melanoma, and to define the potential role of the combination with mutant BRAF inhibitors or after BRAF/MEK inhibitors in BRAF V600E/K mutant tumors, in individuals with advanced melanoma who experience the development or progression of brain metastases after treatment with immune checkpoint inhibitors. The main questions it aims to answer are: * What is the preliminary response rate of defactinib and avutometinib in patients with RAS mutant, BRAF mutant, NF1 mutant, triple RAS/BRAF/NF1 wild type (wt) melanoma (including RAF fusions)? * What is the safety and tolerability of the combination of defactinib, avutometinib, and encorafenib in patients with BRAF V600E/K mutant melanoma with at least one untreated brain metastases? * What is the preliminary response rate of the three drug combination of defactinib, avutometinib, and encorafenib in patients with BRAF V600E/K mutant melanoma.
CONDITIONS
Official Title
Defactinib and Avutometinib, With or Without Encorafenib, for the Treatment of Patients With Brain Metastases From Cutaneous Melanoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older at the time of informed consent
- Provide written informed consent and agree to comply with the study protocol
- Histologically confirmed cutaneous melanoma with brain metastases confirmed by imaging
- Tumor with known RAS, BRAF, NF1 mutation or triple wildtype status confirmed by validated testing
- At least one untreated brain metastasis between 0.5 cm and 4 cm in diameter
- Received at least one prior systemic immunotherapy treatment
- For BRAF V600E/K cohort, may have received prior BRAF or MEK inhibitor therapy
- ECOG Performance Status of 0 or 1, or Karnofsky score of 70 or higher
- Adequate bone marrow, liver, kidney, and cardiac function as defined by specific laboratory parameters
- Female participants of childbearing potential must have a negative pregnancy test and use effective contraception during and for 90 days after treatment
- Male participants of reproductive potential must avoid pregnancy in partners during and for 90 days after treatment
- Recovery to baseline or grade 1 or less toxicity from prior treatments except for specific exceptions
You will not qualify if you...
- Receiving other investigational agents
- Prior systemic anti-cancer or investigational therapy within 28 days or five half-lives before starting study treatment
- Symptomatic brain metastases causing neurological symptoms of grade 2 or higher
- Allergy or hypersensitivity to study drugs or their components
- Inability to swallow or retain study medication
- Diagnosis of uveal or mucosal melanoma
- History or current leptomeningeal metastases
- QTcF interval over 450 msec for males or 470 msec for females
- Significant recent bleeding events or intracranial hemorrhage
- Uncontrolled or severe cardiac disease or hypertension
- History of interstitial lung disease or related lung conditions
- Active or uncontrolled autoimmune diseases requiring recent therapy
- Detectable HIV viral load unless controlled by therapy
- Active systemic infections including tuberculosis, hepatitis B or C not meeting specific criteria
- History of bleeding disorders without anticoagulation
- Uncontrolled intercurrent illness or infection
- Conditions that may prevent compliance with study procedures
- Active skin disorders needing systemic therapy in past year
- History of rhabdomyolysis
- Significant ocular disorders affecting monitoring or safety
- Hypersensitivity to active or inactive ingredients of study drugs
- Use of medications that strongly interact with study drugs within 14 days before or during treatment
- Concurrent use of warfarin
- Use of prohibited medications including other anticancer therapies without proper washout
- Diagnosis of another malignancy within 2 years unless considered low risk or adequately treated
- Any condition judged by the investigator to contraindicate participation due to safety or compliance concerns
- Medical, psychiatric, or cognitive conditions limiting ability to consent or comply with the study
AI-Screening
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Trial Site Locations
Total: 2 locations
1
University of Iowa
Iowa City, Iowa, United States, 52242
Actively Recruiting
2
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Actively Recruiting
Research Team
R
Rachel Kingsford
CONTACT
Y
Yuri Kida
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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