• Age ≥ 1 year

• Histologic diagnosis of a differentiated thyroid cancer, s/p 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 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 neurotrophic tyrosine receptor kinase (NTRK) (NTRK1, NTRK2, or NTRK3) gene fusion in a CLIA/CAP accredited laboratory without known kinase domain resistance mutation

• Lansky/Karnofsky performance status ≥ 50%

• Adequate Organ Function

• A. Bone Marrow Function:

⁃ Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3

⁃ Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)

⁃ Hemoglobin ≥ to 8.0 g/dL at baseline (may receive red blood cell (RBC) 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 as follows:

• Age Maximum Serum Creatinine (mg/dL) Male Female 1 to \< 2 years 0.6 0.6 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1 1 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.5

• ≥ 16 years 1.7 1.7

• C. Adequate Liver Function

⁃ Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age.

⁃ Serum glutamic-pyruvic transaminase (SGPT) (ALT) ≤ 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.

⁃ Serum albumin ≥ 2 g/dL

• Female patients of reproductive potential must agree to use a highly effective contraceptive method for the duration of study therapy and for at least one month after the final dose of larotrectinib. Males of reproductive potential with a non-pregnant female partner of child-bearing potential must use a highly effective contraception for the duration of the study and for at least one month after the final dose of larotrectinib.