NEO- and Adjuvant Targeted Therapy in Braf-mutated Anaplastic Cancer of the Thyroid (NEO-ATACT Study)

Inclusion Criteria: 1. Informed consent. 2. Age over 18 years old. 3. World Health Organization (WHO) Performance Status 0 or I. 4. Histologically confirmed ATC (centrally reviewed). 5. Confirmed presence of BRAFV600E/K mutation in primary tumor tissue. 6. No distant metastases (M0). 7. Free or secured airway. 8. Able to swallow pills. 9. Patients must have undergone complete disease staging including: PET-CT scan and CT-neck/thorax/abdomen. 10. No prior anticancer systemic treatment (including chemotherapy, immunotherapy, oncolytic viral therapy, other systemic therapies). 11. No prior radiotherapy to site of interest. 12. Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥ 1.0x109/L, Platelets ≥ 100 x109/L, Hemoglobin ≥ 6.5 mmol/L, AST ≤ 2.5 x ULN, ALT ≤ 2.5 x ULN, Total bilirubin ≤ 1.5 X ULN, INR and PTT in normal range, LDH \< 2xULN. Serum creatinine ≤ 1.5 × ULN; or calculated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula; or estimated glomerular filtration rate \> 50 mL/min/1.73m2. 13. Absence of additional severe and/or uncontrolled concurrent disease. Exclusion Criteria: 1. No informed consent. 2. History of cancer within 2 years from diagnosis of ATC (exception: basal cell skin cancer, in situ carcinoma). 3. Poorly differentiated transformation of previous differentiated thyroid cancer. 4. Presence of distant metastases. 5. Underlying medical conditions that, in the Investigator's opinion, will make the administration of study treatment hazardous or obscure the interpretation of toxicity determination or adverse events 6. History of congestive heart failure, active cardiac conditions, including unstable coronary syndromes, significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia. 7. Pregnancy or nursing.