Actively Recruiting
Phase II Trial of Avutometinib and Defactinib in RAF Dimer-Driven Radioiodine-Refractory Differentiated and Anaplastic Thyroid Cancer
Led by Memorial Sloan Kettering Cancer Center · Updated on 2026-03-27
30
Participants Needed
7
Research Sites
N/A
Total Duration
On this page
Sponsors
M
Memorial Sloan Kettering Cancer Center
Lead Sponsor
V
Verastem, Inc.
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating whether the combination of avutometinib and defactinib can effectively treat people with RAF dimer-driven radioiodine-refractory differentiated thyroid cancer or anaplastic thyroid cancer. The study also aims to determine if these treatments are safe and cause only mild side effects. This is a Phase II clinical trial sponsored by Memorial Sloan Kettering Cancer Center. Participants receive treatment with avutometinib at 3.2 mg twice weekly and defactinib at 200 mg twice daily, following a schedule of three weeks on treatment and one week off. Two groups are included: one with radioiodine-refractory differentiated thyroid cancer, and another with anaplastic thyroid cancer, both having specific genetic alterations. The study does not involve randomization or blinding. Throughout the study, participants will be monitored for their overall response rate up to two years. Researchers will assess tumor response, side effects, heart function, laboratory tests, and genetic markers. Participants must undergo biopsies for research, provide tissue samples, and attend regular visits for evaluations. The study continues until disease progression or unacceptable side effects occur, with ongoing safety monitoring.
CONDITIONS
Brief Title
A Study of Avutometinib and Defactinib in People With Thyroid Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 18 years or older
- Patients with RAF dimer-driven radioiodine-refractory recurrent or metastatic differentiated thyroid cancer (Cohort A) or anaplastic thyroid carcinoma (Cohort B)
- Confirmation of specific genetic alterations in tumor tissue from a certified laboratory
- For Cohort A: Progressive disease within 14 months prior to enrollment
- For Cohort A: Recurrent or metastatic disease not suitable for curative surgery or radiation
- Measurable disease according to RECIST v1.1
- ECOG performance status of 0 or 1
- No recent thyroid cancer treatments as defined by protocol timelines
- Ability to swallow and retain oral medication without significant gastrointestinal issues
- Adequate recovery from prior treatment toxicities to at least Grade 1 (except certain exceptions)
- Availability of tumor tissue for research biopsies or acceptable alternatives
- Baseline heart function within specific limits
- Adequate laboratory values as specified
You will not qualify if you...
- Symptomatic untreated brain or leptomeningeal metastases
- Prior treatment with MEK 1/2 inhibitors, FAK inhibitors, or inhibitors targeting Class II/III BRAF alterations (with some exceptions)
- Recent systemic investigational anti-cancer therapy within 4 weeks
- Major surgery within 4 weeks, minor surgery within 2 weeks, or radiotherapy within 1 week prior to study drug
- Use of warfarin or certain anticoagulants without proper adjustments
- Use of strong CYP3A4, CYP2C9, or P-glycoprotein inhibitors or inducers
- History or risk factors for glaucoma, retinal vein occlusion, or retinal pathology
- Uncontrolled or treatment-refractory hypertension
- Active hepatitis B infection or known HIV or active hepatitis C infection
- Recent severe COVID-19 infection
- History of rhabdomyolysis
- Significant heart failure, recent heart attack, unstable arrhythmias, or severe lung disease
- Inability to swallow oral medication or impaired gastrointestinal absorption
- Any other medical condition posing high risk for toxicity
- Pregnancy or breastfeeding
- Known hypersensitivity to study drug components
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 3-week cycles on treatment and 1-week off cycles until disease progression or discontinuation
Participants receive Avutometinib 3.2 mg twice weekly and Defactinib 200 mg twice daily in cycles of 3 weeks on treatment followed by 1 week off.
Regular visits during treatment cycles as per protocol
Trial Site Locations
Total: 7 locations
1
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, United States, 07920
Actively Recruiting
2
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, United States, 07748
Actively Recruiting
3
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, United States, 07645
Actively Recruiting
4
Memorial Sloan Kettering Cancer Center Suffolk - Commack (Limited Protocol Activities)
Commack, New York, United States, 11725
Actively Recruiting
5
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, United States, 10604
Actively Recruiting
6
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, United States, 10065
Actively Recruiting
7
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Rockville Centre, New York, United States, 11553
Actively Recruiting
Research Team
A
Alan Ho, MD, PhD
E
Eric Sherman, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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