Method of Treating Cancer using a cMet and AXL Inhibitor and an ErbB Inhibitor
The present invention relates to a method of treating cancer in a patient comprising administering to the patient therapeutically effective amounts of: a) a compound of formula A: or a pharmaceutically acceptable salt thereof, wherein R 1 -R 4 , p, and q are as defined; and (b) an erbB inhibitor that inhibits erbB-1 or erbB-2 or erbB-3 receptor or a combination thereof. The method of the present invention addresses a need in the art with the discovery of a combination therapy that shows evidence of being a more effective therapy than previously disclosed therapies.
1 . A method of treating cancer in a patient comprising administering to the patient therapeutically effective amounts of:
a) a compound of the formula A:
or a pharmaceutically acceptable salt thereof, and
(b) an erbB inhibitor that inhibits erbB-1 or erbB-2 or erbB-3 receptor or a combination thereof, wherein
R 1 is C 1 -C 6 -alkyl;
R 2 is C 1 -C 6 -alkyl or —(CH 2 ) n —N(R 5 ) 2 ;
R 3 is Cl or F;
R 4 is Cl or F;
each R 5 is independently C 1 -C 6 -alkyl or, together with the nitrogen atom to which they are attached, form a morpholino, piperidinyl, or pyrazinyl group;
n is 2, 3, or 4;
p is 0 or 1; and
q is 0, 1, or 2.
2 . The method of claim 1 wherein q is 0 or 1; and R 1 is methyl.
3 . The method of claim 1 wherein the compound of formula A is represented by a compound of formula I:
or a pharmaceutically acceptable salt thereof.
4 . The method of claim 3 wherein the erbB inhibitor is a compound of formula II:
or a pharmaceutically acceptable salt thereof.
5 . The method of claim 4 wherein the erb inhibitor is a ditosylate salt or a ditosylate monohydrate salt of the compound of formula II.
6 . The method of claim 3 wherein the erbB inhibitor is a compound of formula III:
or a pharmaceutically acceptable salt thereof.
7 . The method of claim 3 wherein the erbB inhibitor is a compound of formula IV:
8 . The method of claim 3 wherein the erbB inhibitor is trastuzumab.
9 . The method of claim 3 wherein the erbB inhibitor is cetuximab.
10 . The method of claim 3 wherein the erbB inhibitor is a monoclonal antihuman erbB3 antibody.
11 . The method of claim 3 wherein the cancer is gastric, lung, esophageal, head and neck, skin, epidermal, ovarian, or breast cancer.
12 . A method of treating a patient suffering from breast cancer or head and neck cancer comprising administering to the patient a therapeutically effective amount of a compound of formula I:
or a pharmaceutically acceptable salt thereof.
13 . The method of claim 12 which is a method of treating a patient suffering from breast cancer.
14 . The method of claim 12 which is a method of treating a patient suffering from head and neck cancer.
15 . The method of claim 1 , wherein a pharmaceutically acceptable excipient is included with the compound or pharmaceutically acceptable salt of formula A; or the erbB inhibitor; or a combination thereof.