HPK1 inhibitors and uses thereof
The invention provides a compound represented by structural formula (I) or formula (II), or a pharmaceutically acceptable salt or a stereoisomer thereof useful for treating diseases (such as cancer) that are treatable by inhibiting HPK1 activity.
1 . A compound represented by Formula I,
or a pharmaceutically acceptable salt, or a stereoisomer thereof.
2 . The compound of claim 1 , represented by Formula IA,
or a pharmaceutically acceptable salt.
3 . Ne compound of claim 1 , represented by Formula IB,
or a pharmaceutically acceptable salt.
4 . A compound represented by Formula IIA,
or a pharmaceutically acceptable salt.
5 . A compound represented by Formula IIB,
or a pharmaceutically acceptable salt.
6 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt or a stereoisomer thereof, and a pharmaceutically acceptable carrier.
7 . A combination comprising a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, and one or more therapeutically active co-agents.
8 . A method for treating a subject with cancer, comprising administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, or a stereoisomer thereof.
9 . The method of claim 8 , wherein the cancer is selected from breast cancer, colorectal cancer, lung cancer, ovarian cancer, and pancreatic cancer.
10 . A method of inhibiting HPK1 activity in a subject in need thereof, said method comprising administering to the subject an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof.
11 . The method of claim 10 , wherein the subject has a cancer, and wherein the cancer is treated.
12 . The method of claim 11 , wherein the cancer is selected from breast cancer, colorectal cancer, lung cancer, ovarian cancer, and pancreatic cancer.
13 . A method for treating a subject with cancer, comprising administering to the subject a therapeutically effective amount of the compound of claim 1 in combination with an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L1 inhibitor, or a CTLA-4 inhibitor.
14 . The method of claim 13 , wherein the immune checkpoint inhibitor is a bispecific monoclonal antibody or an antigen binding fragment thereof specific for PD-1 and PD-L1, or CTLA-4.
15 . The method of claim 14 , wherein the cancer is selected from breast cancer, colorectal cancer, lung cancer, ovarian cancer, and pancreatic cancer.
16 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 5 or a pharmaceutically acceptable salt or a stereoisomer thereof, and a pharmaceutically acceptable carrier.
17 . A combination comprising a therapeutically effective amount of the compound of claim 5 or a pharmaceutically acceptable salt or a stereoisomer thereof, and one or more therapeutically active co-agents.
18 . A method for treating a subject with cancer, comprising administering to the subject an effective amount of a compound of claim 5 , or a pharmaceutically acceptable salt, or a stereoisomer thereof.
19 . The method of claim 18 , wherein the cancer is selected from breast cancer, colorectal cancer, lung cancer, ovarian cancer, and pancreatic cancer.
20 . A method of inhibiting HPK1 activity in a subject in need thereof, said method comprising administering to the subject an effective amount of compound of claim 5 , or a pharmaceutically acceptable salt or a stereoisomer thereof.
21 . A method of claim 20 , wherein the subject has cancer, and wherein the cancer is treated.
22 . A method of claim 21 , wherein the cancer is selected from that of breast cancer, colorectal cancer, lung cancer, ovarian cancer, and pancreatic cancer.
23 . A method for treating a subject with cancer, comprising administering to the subject a therapeutically effective amount of the compound of claim 5 in combination with an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L1 inhibitor, or a CTLA-4 inhibitor.
24 . The method of claim 23 , wherein the immune checkpoint inhibitor is a bispecific monoclonal antibody or an antigen binding fragment thereof specific for PD-1 and PD-L1, or CTLA-4.
25 . The method of claim 24 , wherein the cancer is selected from breast cancer, colorectal cancer, lung cancer, ovarian cancer, and pancreatic cancer.