• Histologically-confirmed differentiated (including poorly differentiated) thyroid cancer that is either locally advanced or metastatic.

• Age \> 18 years.

• Life expectancy \> 12 weeks.

• Documented radiological progression by RECIST 1.1 in last 12 months.

• Radioiodine refractory (at least one of):

∙ one measurable lesion without radioiodine uptake on 131I scan,

‣ at least one measurable lesion that had progressed by RECIST criteria within 12 months of 131I therapy despite 131I avidity at time of treatment, or

‣ cumulative treatment with \>24 GBq (600 mCi) of 131I.

• At least one evaluable lesion as per RECIST v1.1 that has not been treated with local radiation therapy within 3 months prior to the first dose of TKI. Irradiated lesions can only be included as an evaluable lesion if it has shown radiological progression as per RECIST v1.1 on subsequent imaging following irradiation.

• NRAS or BRAF V600E mutation tested by NGS in a NATA accredited laboratory or by recognised sequencing platform.

• ECOG 0-1.

• Informed consent.

⁃ Adequate haematological and biochemical parameters:

• Haemoglobin ≥ 9g/dL

∙ Neutrophils ≥ 1.5 x 109/L

∙ Platelets ≥ 100 x 109/L

∙ INR ≤ 1.4

∙ Serum Creatinine ≤ 1.3 x ULN

∙ Estimated Creatinine Clearance ≥ 30 ml/min (by Cockcroft Gault Formula)

∙ Serum ALT and AST ≤ 2.5 x ULN

∙ Serum Total Bilirubin ≤ 1.5 x ULN.

∙ TSH suppression \<0.1mU/L or otherwise consistent with 2015 ATA Guidelines on Thyroid Cancer