A Study of Avutometinib and Defactinib in People With Thyroid Cancer

This study is testing a combination of two targeted drugs — avutometinib and defactinib — in patients with thyroid cancer that has specific genetic changes driving tumor growth (RAF dimer-driven disease) and is no longer responding to standard treatments including radioactive iodine. **You may be eligible if:** - You are 18 or older - You have differentiated thyroid cancer (such as papillary or follicular) that is no longer responding to radioactive iodine (Cohort A), OR you have anaplastic thyroid cancer (Cohort B) - Your tumor has a specific genetic mutation (such as RAS, NF1, RET rearrangement, NTRK, ALK, or non-V600E BRAF alteration) - You have measurable disease on imaging - You are in good health (ECOG 0–1) **You may NOT be eligible if:** - You have had recent radioactive iodine or targeted therapy (within the required washout period) - You do not have the required genetic alteration - You are pregnant or nursing - Your disease doesn't meet the criteria for your specific cohort Talk to your doctor to see if this trial is right for you.