A new drug combination for specific types of thyroid cancer

Phase II trial of avutometinib plus defactinib in RAF dimer-driven thyroid cancers

NIH-funded research Sloan-Kettering Inst Can Research · NIH-11193449

This research is testing a combination of two medicines, avutometinib and defactinib, for people with rare and aggressive forms of thyroid cancer that have specific genetic changes.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionSloan-Kettering Inst Can Research NIH-funded
Lab location1 site (New York, United States)
Project IDNIH-11193449 on NIH RePORTER

What this research studies

Two rare types of thyroid cancer, radioiodine-refractory differentiated thyroid cancer and anaplastic thyroid cancer, currently have very poor outcomes. While some targeted treatments exist for other genetic changes, therapies for tumors driven by RAF dimers (like RAS, NF1, and non-V600 BRAF mutations) are still needed. This study uses avutometinib, a new type of MEK inhibitor, which has shown promise in RAS-mutant tumors. However, it can lead to resistance, so researchers are combining it with defactinib to block a pathway called FAK that contributes to this resistance.

Who could benefit from this research

Good fit: Ideal candidates are patients with radioiodine-refractory, recurrent, or metastatic differentiated thyroid cancer, or anaplastic thyroid cancer, whose tumors are driven by RAF dimer-activating mutations like RAS, NF1, or non-V600 BRAF.

Not a fit: Patients whose thyroid cancers do not have these specific RAF dimer-activating genetic mutations may not benefit from this particular treatment approach.

Why it matters

Potential benefit: If successful, this drug combination could offer a new and more effective treatment option for patients with these aggressive and hard-to-treat thyroid cancers.

How similar studies have performed: Avutometinib alone has shown promising activity against RAS-mutant tumors, but this combination with defactinib is designed to overcome resistance mechanisms observed with single-drug therapy.

Where this research is happening

New York, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.