METHODS OF TREATING A DISEASE OR DISORDER ASSOCIATED WITH BRUTON'S TYROSINE KINASE
The present invention provides methods of treating, stabilizing or lessening the severity or progression of a disease or disorder associated with BTK.
1 . A method of treating, stabilizing or lessening the severity or progression of one or more diseases and conditions associated with BTK comprising administering to a patient in need thereof an irreversible BTK inhibitor and lenalidomide, wherein the irreversible BTK inhibitor has not more than about 50% inhibition of a kinase selected from c-Kit, PDGFRa, RIPK2, HCK, EPHA6, LYN, CSK, LCK, ZAK/MLTK, LYN B, FRK/PTK5, FYN, BRAF, RIPK3, ARAF and SRMS, or combinations thereof.
2 . The method according to claim 1 , wherein the irreversible BTK inhibitor has not more than about 30% inhibition of a kinase selected from c-Kit, RIPK2, HCK, EPHA6, LYN, CSK, ZAK/MLTK, LYN B, FRK/PTK5, FYN, BRAF, RIPK3, ARAF and SRMS, or combinations thereof.
3 . The method according to claim 1 , wherein the irreversible BTK inhibitor has not more than about 10% inhibition of a kinase selected from EPHA6, LYN B, FRK/PTK5, BRAF, RIPK3, ARAF and SRMS, or combinations thereof.
4 . The method according to claim 1 , wherein the irreversible BTK inhibitor has a percent inhibition of LYN that is not more than about 20-30%.
5 . A method of treating, stabilizing or lessening the severity or progression of one or more diseases and conditions associated with BTK comprising administering to a patient in need thereof Compound 1 (N-(3-(5-fluoro-2-(4-(2-methoxyethoxyl)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide):
or a pharmaceutically acceptable salt thereof, lenalidomide and an anti-CD20 antibody.
6 . The method according to claim 5 , wherein the disease or condition associated with BTK is selected from chronic lymphocytic leukemia and small lymphocytic lymphoma.
7 . The method according to claim 6 , wherein Compound 1 is administered twice a day.
8 . The method according to claim 7 , wherein Compound 1 is administered on each day of a 28-day cycle.
9 . The method according to claim 8 , wherein the anti-CD20 antibody is rituximab.
10 . The method according to claim 9 , wherein rituximab is administered once during a 28-day cycle.
11 . The method according to claim 10 , wherein rituximab is administered as an intravenous infusion.
12 . The method according to claim 11 , wherein lenalidomide is administered once a day starting with the second 28-day cycle.
13 . The method according to claim 7 , wherein Compound 1 is in the form of a benzenesulfonic acid salt.
14 . The method of claim 13 , wherein each of Compound 1 and lenalidomide is administered as an oral dosage form.
15 . A method of preventing, treating, stabilizing or lessening the severity or progression of a disease or disorder selected from the group consisting of chronic lymphocytic leukemia and small lymphocytic lymphoma, the method comprising administering to a patient in need thereof therapeutically effective amounts of each of Compound 1, or a pharmaceutically acceptable salt thereof, lenalidomide and an anti-CD20 antibody, wherein the therapeutically effective amount of Compound 1 is about 750 mg to about 1000 mg per day.
16 . The method according to claim 15 , wherein the anti-CD20 antibody is rituximab.
17 . The method according to claim 15 , wherein the therapeutically effective amount of Compound 1 is about 375 mg BID.
18 . The method according to claim 15 , wherein the therapeutically effective amount Compound 1 is about 500 mg BID.
19 . The method according to claim 16 , wherein the therapeutically effective amount of rituximab is about 375 mg/m 2 .
20 . The method according to claim 16 , wherein the therapeutically effective amount of rituximab is about 500 mg/m 2 .
21 . The method according to claim 15 , wherein lenalidomide is administered starting with the second 28-day cycle.
22 . The method according to claim 21 , wherein the therapeutically effective amount of lenalidomide is about 5 mg.
23 . The method according to claim 21 , wherein the therapeutically effective amount of lenalidomide is about 10 mg.
24 . A system for treating, stabilizing or lessening the severity of one or more diseases or conditions associated with BTK, the system comprising Compound 1, or a pharmaceutically acceptable salt thereof, lenalidomide and an anti-CD20 antibody.
25 . The system according to claim 24 , wherein the anti-CD20 antibody is rituximab.