COMBINATION THERAPIES FOR TREATING CANCERS
Provided herein are methods that relate to a therapeutic strategy for treatment of cancer, including hematological malignancies. In particular, the methods include administration entospletinib and a Bcl-2 inhibitor, such as venetoclax, navitoclax, and ABT-737.
1 . A pharmaceutical composition comprising a therapeutically effective amount of a Syk inhibitor and a therapeutically effective amount of a Bcl-2 inhibitor, wherein:
the Syk inhibitor is a compound of formula A1:
or a pharmaceutically acceptable salt or hydrate thereof; and
the Bcl-2 inhibitor is selected from the group consisting of a compound of Formula B1, a compound of Formula B2, and a compound of Formula B3:
or a pharmaceutically acceptable salt thereof.
2 . The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable salt of the Syk inhibitor is a mesylate salt, or a hydrate thereof.
3 . The pharmaceutical composition of claim 2 , wherein the mesylate salt is a mono-mesylate salt or a bis-mesylate salt, or a combination thereof.
4 . The pharmaceutical composition of claim 1 , wherein the Bcl-2 inhibitor is a compound of formula B1:
or a pharmaceutically acceptable salt thereof.
5 . The pharmaceutical composition of claim 4 , wherein the compound of Formula B1 is of a form selected from the group consisting of a free base anhydrate, a free base dichloromethane solvate, a free base ethyl acetate solvate, a free base acetonitrile solvate, a free base acetone solvate, a hydrochloride, a hydrochloride hydrate, a free base sulfate, and a free base tetrahydrofuran.
6 . The pharmaceutical composition of claim 1 , wherein the Bcl-2 inhibitor is a compound of formula B2:
or a pharmaceutically acceptable salt thereof.
7 . The pharmaceutical composition of claim 1 , wherein the Bcl-2 inhibitor is a compound of formula B3:
or a pharmaceutically acceptable salt thereof.
8 . The pharmaceutical composition of claim 7 , wherein the Bcl-2 inhibitor is a bis-HCl salt of the compound of Formula B3.
9 . The pharmaceutical composition of claim 1 , wherein the Syk inhibitor is formulated for administration intravenously, intramuscularly, parenterally, nasally or orally.
10 . The pharmaceutical composition of claim 1 , wherein the Bcl-2 inhibitor is formulated for administration intravenously, intramuscularly, parenterally, nasally or orally.
11 - 19 . (canceled)
20 . A kit comprising:
(i) a pharmaceutical composition comprising a therapeutically effective amount of a Syk inhibitor, wherein the Syk inhibitor is a compound of Formula A1:
or a pharmaceutically acceptable salt or hydrate thereof;
(ii) a pharmaceutical composition comprising a therapeutically effective amount of a Bcl-2 inhibitor, wherein the Bcl-2 inhibitor is selected from the group consisting of a compound of Formula B1, a compound of Formula B2, and a compound of Formula B3:
or a pharmaceutically acceptable salt thereof.
21 . The kit of claim 20 , further comprising a package insert containing instructions for use of the pharmaceutical compositions in treating a cancer.