Lenvatinib and Pembrolizumab for the Treatment of Stage IVB Locally Advanced and Unresectable or Stage IVC Metastatic Anaplastic Thyroid Cancer

PRIMARY OBJECTIVE: I. Demonstrate the efficacy (overall survival \[OS\]) of lenvatinib plus pembrolizumab in treatment naive patients. SECONDARY OBJECTIVES: I. Determine the response rate and progression-free survival (PFS) in patients treated with lenvatinib plus pembrolizumab. II. Establish safety for concurrent administration of lenvatinib plus pembrolizumab. EXPLORATORY OBJECTIVE: I. Translational endpoints: cell-free deoxyribonucleic acid (DNA) changes and immune biomarkers will be studied. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive lenvatinib orally (PO) daily on days 1-21. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.