Combinations of AKT and MEK inhibitor compounds, and methods of use
The invention provides combinations comprising a) compound of formula I: (formula I), or a pharmaceutically acceptable salt thereof; and another agent selected from GDC-0973, PD-0325901, or a pharmaceutically acceptable salt thereof. The combinations are particularly useful for treating hyperproliferative disorders, such as cancer.
1. A method for treating melanoma in a mammal, comprising administering to the mammal a combination of a compound of formula I:
or a pharmaceutically acceptable salt thereof; and an agent selected from GDC-0973 or a pharmaceutically acceptable salt thereof, wherein the combination is present in an amount effective to provide a synergistic effect in treating the melanoma, wherein the combination is present at a ratio of from 1:1 to 16:1 of the compound of formula I or a pharmaceutically acceptable salt thereof: GDC-0973 or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the melanoma is associated with PTEN mutation.
3. The method of claim 1 , wherein the melanoma is associated with AKT mutation, overexpression or amplification.
4. The method of claim 1 , wherein the melanoma is associated with PI3K mutation.
5. The method of claim 1 , wherein the melanoma is associated with Her2/ErbB2 amplification.
6. The method of claim 1 , wherein the compound of formula I or the salt thereof is administered simultaneously with the GDC-0973 or a pharmaceutically acceptable salt thereof.
7. The method of claim 1 , wherein the compound of formula I or the salt and the GDC-0973 or a pharmaceutically acceptable salt thereof are administered sequentially.
8. The method of claim 1 , wherein administration of the GDC-0973 or a pharmaceutically acceptable salt thereof begins about 1 to about 10 days before administration of the compound of formula I or the salt.
9. The method of claim 1 , wherein administration of the compound of formula I or the salt thereof begins about 1 to about 10 days before administration of the GDC-0973 or a pharmaceutically acceptable salt thereof.
10. The method of claim 1 , wherein administration of the compound of formula I or the salt thereof and administration of the GDC-0973 or a pharmaceutically acceptable salt thereof begins on the same day.