Actively Recruiting
A Study of Avutometinib and Defactinib in People With Thyroid Cancer
Led by Memorial Sloan Kettering Cancer Center · Updated on 2026-03-27
30
Participants Needed
7
Research Sites
208 weeks
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
The researchers are doing this study to find out if the combination of avutometinib and defactinib is an effective treatment for RAF dimer-driven radioiodine-refractory differentiated thyroid cancer or anaplastic thyroid cancer. The researchers will also test whether avutometinib and defactinib is a safe treatment that causes few or mild side effects.
CONDITIONS
Official 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
- Cohort A: Patients with RAF dimer-driven radioiodine-refractory differentiated thyroid cancer of follicular origin
- Cohort B: Patients with RAF dimer-driven anaplastic thyroid carcinoma
- Confirmation of specific genetic alterations (e.g., RAS mutation, NF1 mutation, RET rearrangement, NTRK rearrangement, ALK rearrangement, Class 2 or 3 BRAF alterations) in thyroid tumors
- Cohort A: Evidence of progressive disease within 14 months before enrollment
- Cohort A: Recurrent or metastatic disease not suitable for curative surgery or radiation
- Patients with measurable disease by RECIST v1.1
- ECOG performance status of 0 or 1
- For Cohort A: No prior radioiodine therapy within 6 months, no external beam radiation therapy within 1 week, and no chemotherapy or targeted therapy within 4 weeks before starting study treatment
- Cohort A: Radioiodine-refractory disease defined by lifetime radioiodine dose, scan results, or presence of FDG avid lesions
- Ability to swallow and retain oral pills without significant gastrointestinal problems
- Recovery from prior treatment toxicities to at least Grade 1 except alopecia and peripheral neuropathy grade 2
- Availability of tumor tissue for study biopsies or prior samples
- Agreement to undergo required research biopsies unless medically exempt
- Baseline QTc intervals below specified limits
- Adequate cardiac function with left ventricular ejection fraction above 50%
- Laboratory values within specified limits for blood counts, liver and kidney function, and coagulation parameters
You will not qualify if you...
- Symptomatic untreated brain or leptomeningeal metastases
- Prior treatment with MEK 1/2 inhibitors, Class II/III BRAF inhibitors, or FAK inhibitors (except for radioiodine activity enhancement)
- Systemic investigational anti-cancer therapy within 4 weeks before study treatment
- Major surgery within 4 weeks, minor surgery within 2 weeks, or radiotherapy within 1 week before study treatment
- Current treatment with warfarin
- Use of strong CYP3A4, CYP2C9, or P-glycoprotein inhibitors or inducers during treatment
- History of glaucoma, retinal vein occlusion, or related retinal conditions
- Treatment-resistant high blood pressure
- Active hepatitis B infection
- Known HIV or active hepatitis C infection
- Recent severe COVID-19 infection within 28 days before treatment
- History of rhabdomyolysis
- Serious heart conditions including congestive heart failure, recent heart attack, unstable arrhythmias, or severe lung disease
- Inability to swallow oral medications or significant gastrointestinal absorption problems
- Any other medical condition posing high risk for toxicity as judged by the investigator
- Pregnancy or breastfeeding
- Allergy to study drug ingredients including mannitol, magnesium stearate, or hydroxypropyl methylcellulose shells
AI-Screening
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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
CONTACT
E
Eric Sherman, MD
CONTACT
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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