• Age 2-21 years, inclusive

• Histologic diagnosis of a differentiated thyroid cancer, status post thyroidectomy and adequate local therapy (e.g., lymph node dissection as per standard of care) for metastatic disease in the neck in the opinion of the treating investigator

• Anatomically evaluable disease on chest CT (Computed Tomography) meeting one of the following criteria (obtained within 90 days of enrollment):

• A. multiple (\> 10) noncalcified solid pulmonary nodules visible on CT and/or B. enlarging, discrete pulmonary nodules visible on CT of any number consistent with metastatic disease

• Identification of an activating RET gene alteration (fusion or mutation). The RET alteration result should be generated from a laboratory with specific certifications (depending on country requirement) that clearly denotes the presence of a RET alteration without known kinase domain resistance mutation

• Lansky/Karnofsky performance status \>50%

• Adequate Organ Function

• A. Bone Marrow Function:

⁃ Peripheral absolute neutrophil count (ANC) ≥1500/µL

⁃ Platelet count ≥ 100,000/µL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)

⁃ Hemoglobin ≥ 9.0 g/dL at baseline (may receive Red Blood Cell transfusions).

• B. Adequate Renal Function: Creatinine clearance or radioisotope Glomerular Filtration Rate (GFR) ≥ 70 mL/min/1.73 m2 or a maximum serum creatinine based on age/gender.

• C. Adequate Liver Function

⁃ Bilirubin (sum of conjugated + unconjugated) \< / = 1.5 x upper limit of normal (ULN) for age. Except participants with a documented history of Gilbert syndrome who must have a total bilirubin level of \<3.0X ULN

⁃ Alanine aminotransferase (ALT) \<2.5X ULN OR \<5x ULN if the liver has tumor involvement. For the purpose of this study, the ULN for ALT is 45 U/L.

⁃ Serum albumin ≥ 2 g/dL

• Patient must have normal serum potassium, calcium, and magnesium levels (may be receiving supplements)

• Men with partners of childbearing potential or women of childbearing potential must agree to use a highly effective contraceptive method during treatment with study drug and for 6 months following the last dose of study drug. Selpercatinib could impair fertility in males and females. Advise women not to breastfeed during treatment with selpercatinib and for 1 week following the final dose

• Women of childbearing potential must have a negative pregnancy test (serum or urine, consistent with local regulations) documented within 24 hours prior to treatment with study drug and at least monthly while on study treatment