Study on Avutometinib and Defactinib for Treating Thyroid Cancer

Inclusion Criteria

• Patients with specific types of thyroid cancer that are resistant to radioiodine treatment or are anaplastic.
• For Cohort A: Patients must have a confirmed diagnosis of differentiated thyroid cancer of follicular origin, including various subtypes.
• For Cohort B: Patients must have anaplastic thyroid carcinoma.
• The cancer must have certain genetic changes, such as RAS or NF1 mutations, or specific rearrangements like RET or ALK.
• For Cohort A: Evidence of cancer progression within 14 months before joining the study.
• For Cohort A: Cancer must have returned or spread and cannot be treated with surgery or radiation.
• Patients can have had any number of previous treatments.
• Must have measurable disease according to specific criteria.
• Age 18 years or older.
• Good overall health with a performance status of 0 or 1.
• For Cohort A: No recent treatments for thyroid cancer, including radioiodine therapy, radiation, or chemotherapy, within specified timeframes before starting the study.
• For Cohort A: Must have radioiodine-refractory disease, meeting specific criteria.
• Must be able to swallow pills and not have significant digestive issues.
• Must have recovered from previous treatment side effects to a certain level.
• Must provide tumor tissue samples for research.
• Must agree to undergo two research biopsies unless exempted for specific reasons.
• Must have a baseline heart rhythm within specified limits.
• Must have adequate heart function.
• Must meet specific blood test criteria for health and organ function.

Exclusion Criteria

• Have untreated or symptomatic brain or leptomeningeal metastases.
• Have previously used certain cancer drugs targeting specific genetic changes, unless used to enhance radioiodine activity.
• Have had investigational cancer therapy within 4 weeks before starting the study.
• Have had major surgery within 4 weeks or minor surgery within 2 weeks before starting the study.
• Are taking warfarin and cannot switch to another blood thinner.
• Are using certain medications that affect drug metabolism.
• Have a history of eye conditions like glaucoma or retinal vein occlusion.
• Have uncontrolled high blood pressure.
• Have active hepatitis B or C infections or HIV.
• Have had COVID-19 symptoms within 28 days before starting the study.
• Have a history of muscle breakdown (rhabdomyolysis).
• Have serious heart or lung conditions.
• Cannot swallow pills or have digestive issues affecting absorption.
• Have any other medical condition that poses a high risk for treatment.
• Are pregnant or breastfeeding.
• Have allergies to certain ingredients in the study drugs.