RET inhibitor for use in treating cancer having a RET alteration
Disclosed herein are methods for treating a subject afflicted with a cancer having an activating RET alteration by administering an effective amount of a selective RET inhibitor, e.g., Compound 1 or pharmaceutically acceptable salts thereof, including, e.g., administering an amount of 60 mg to 400 mg of the selective RET inhibitor once daily.
1. A method of treating a subject with a rearranged during transfection (RET)-altered thyroid cancer, the method comprising orally administering to the subject once daily 200 mg, 300 mg, or 400 mg of Compound 1 or a pharmaceutically acceptable salt thereof, wherein Compound 1 is:
2. The method of claim 1 , wherein the RET-altered thyroid cancer has a RET fusion, wherein the RET fusion partner is selected from the group consisting of CCDC6, PTClex9, NCOA4, TRIM33, ERC1, MBD1, RAB61P2, PRKAR1A, TRIM24, KTN1, GOLGA5, HOOK3, KIAA1468, TRIM27, AKAP13, FKBP15, SPECC1L, TBL1XR1, ACBD5, KIAA1217, and MYH13.
3. The method of claim 1 , wherein the RET-altered thyroid cancer has a RET mutation.
4. The method of claim 3 , wherein the RET mutation is V804L, V804M, or V804E.
5. The method of claim 3 , wherein the RET mutation is M918T.
6. The method of claim 3 , wherein the RET mutation is C609Y, C609S, C609G, C609R, C609F, C609W, C611R, C611S, C611G, C611Y, C611F, C611W, C618S, C618Y, C618R, C618G, C618F, C618W, C620S, C620W, C620R, C620G, C620L, C620Y, C620F, C630A, C630R, C630S, C630Y, C630F, C634W, C634Y, C634S, C634F, C634G, C634L, C634A, or C634T.
7. The method of claim 3 , wherein the RET mutation is L790F.
8. The method of claim 3 , wherein the RET mutation is R844W, R844Q, or R844L.
9. The method of claim 3 , wherein the RET mutation is A883F, A883S, or A883T.
10. The method of claim 3 , wherein the RET mutation is K666E, K666M, or K666N.
11. The method of claim 1 , wherein the RET-altered thyroid cancer is papillary thyroid cancer.
12. The method of claim 1 , wherein the RET-altered thyroid cancer is radioactive iodine (RAI) refractory.
13. The method of claim 1 , wherein the subject is orally administered 200 mg of Compound 1 once daily.
14. The method of claim 1 , wherein the subject is orally administered 300 mg of Compound 1 once daily.
15. The method of claim 1 , wherein the subject is orally administered 400 mg of Compound 1 once daily.
16. A method of treating a subject with a rearranged during transfection (RET)-mutant medullary thyroid cancer (MTC), the method comprising orally administering to the subject once daily 200 mg, 300 mg, or 400 mg of Compound 1 or a pharmaceutically acceptable salt thereof, wherein Compound 1 is:
17. A method of treating a subject with a rearranged during transfection (RET)-altered thyroid cancer, the method comprising orally administering once daily to the subject two or more solid dosage forms each comprising a pharmaceutically acceptable excipient and 100 mg of Compound 1 or a pharmaceutically acceptable salt thereof, wherein Compound 1 is:
18. A method of treating a subject with a rearranged during transfection (RET)-mutant medullary thyroid cancer (MTC), the method comprising orally administering once daily to the subject two or more solid dosage forms each comprising a pharmaceutically acceptable excipient and 100 mg of Compound 1 or a pharmaceutically acceptable salt thereof, wherein Compound 1 is:
19. A method of treating a subject with a rearranged during transfection (RET)-fusion thyroid cancer, the method comprising orally administering to the subject once daily 200 mg, 300 mg, or 400 mg of Compound 1 or a pharmaceutically acceptable salt thereof, wherein Compound 1 is:
20. A method of treating a subject with a rearranged during transfection (RET)-fusion thyroid cancer, the method comprising orally administering once daily to the subject two or more solid dosage forms each comprising a pharmaceutically acceptable excipient and 100 mg Compound 1 or a pharmaceutically acceptable salt thereof, wherein Compound 1 is:
21. The method of claim 1 , wherein the RET-altered thyroid cancer is medullary thyroid cancer.
22. The method of claim 1 , wherein the RET-altered thyroid cancer is differentiated thyroid cancer.
23. The method of claim 1 , wherein the RET-altered thyroid cancer is follicular thyroid cancer.
24. The method of claim 1 , wherein the RET-altered thyroid cancer is anaplastic thyroid cancer.