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 non-small cell lung cancer (NSCLC), the method comprising orally administering to the subject once daily 200 mg, 300 mg, or 400 mg of Compound 1or a pharmaceutically acceptable salt thereof, wherein Compound 1 is:
2. The method of claim 1 , wherein the NSCLC has a RET-gene rearrangement.
3. The method of claim 2 , wherein the RET-gene rearrangement is a RET fusion.
4. The method of claim 3 , wherein the RET fusion is selected from CLIP1, PIBF1, BCR, FGFRIOP, CEP55, CUX1, MYH13, PTClex9, MPRIP, CCDC6, KIF5B, TRIM33, MBD1, RAB61P2, PRKAR1A, TRIM24, KTN1, HOOK3, TRIM27, AKAP13, FKBP15, ERC1, KIAA1468, KIAA1217, NCOA4, GOLGA5, SPECC1L, TBL1XR1 and ACBD5.
5. The method of claim 3 , wherein the RET fusion is selected from CCDC6, KIF5B, TRIM33, TRIM24, and NCOA4.
6. The method of claim 3 , wherein the RET fusion is KIF5B.
7. The method of claim 3 , wherein the RET fusion is CCDC6.
8. The method of claim 1 , wherein the NSCLC is metastatic NSCLC.
9. The method of claim 1 , wherein the subject was previously treated with platinum.
10. The method of claim 9 , wherein the platinum is selected from cisplatin and carboplatin.
11. The method of claim 1 , wherein the subject was previously treated with cabozantinib or vandetanib or both.
12. The method of claim 8 , wherein the subject is orally administered 300 mg of Compound 1 once daily.
13. The method of claim 8 , wherein the subject is orally administered 400 mg of Compound 1 once daily.
14. The method of claim 1 , wherein the subject is orally administered 200 mg of Compound 1 once daily.
15. The method of claim 1 , wherein the Compound 1 or a pharmaceutically acceptable salt thereof is administered as one or more solid dosage forms.
16. The method of claim 15 , wherein the one or more solid dosage forms are tablets.
17. The method of claim 15 , wherein the one or more solid dosage forms are capsules.
18. A method of treating a subject with a metastatic rearranged during transfection (RET)-altered non-small cell lung cancer (NSCLC) comprising a RET fusion, the method comprising orally administering to the subject once daily 300 mg of Compound 1 or a pharmaceutically acceptable salt thereof, wherein Compound 1 is:
19. A method of treating a subject with a metastatic rearranged during transfection (RET)-altered non-small cell lung cancer (NSCLC) comprising a RET fusion, the method comprising orally administering to the subject once daily 400 mg of Compound 1 or a pharmaceutically acceptable salt thereof, wherein Compound 1 is: