Pharmaceutical Combinations

Abstract

A pharmaceutical combination comprising: (a) a phosphatidylinositol-3-kinase inhibitor selected from 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine, (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or any pharmaceutically acceptable salt thereof and (b) a gonadorelin agonist and, optionally, (c) an antiestrogen agent, particularly for use in the treatment or prevention of a cancer; uses of such a combination in the preparation of a medicament for the treatment or prevention of a cancer; pharmaceutical compositions of the combination of said therapeutic agents and methods of treating a cancer in a subject comprising administering to said subject a therapeutically effective amount of such a combination.

1 . A pharmaceutical combination comprising: (a) a phosphatidylinositol-3-kinase (PI3K) inhibitor selected from 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine, (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or any pharmaceutically acceptable salt thereof, (b) a gonadorelin agonist, and, optionally, (c) an antiestrogen agent. 
     
     
         2 . A pharmaceutical combination according to  claim 1 , wherein the gonadorelin agonist is selected from abarelix, goserelin, buserelin, or any pharmaceutically acceptable salts thereof. 
     
     
         3 . A pharmaceutical combination according to  claim 2 , wherein the gonadorelin agonist is goserelin acetate. 
     
     
         4 . A pharmaceutical combination according to  claim 1 , wherein the pharmaceutical combination comprises an antiestrogen agent selected from tamoxifen, fulvestrant, raloxifene, raloxifene hydrochloride or any pharmaceutically acceptable salts thereof. 
     
     
         5 . A pharmaceutical combination according to  claim 1 , wherein the pharmaceutical combination comprises the antiestrogen agent tamoxifen or any pharmaceutically acceptable salt thereof. 
     
     
         6 . A pharmaceutical combination according to  claim 1 , wherein the pharmaceutical combination comprises gonadorelin agonist goserelin acetate and the antiestrogen agent is tamoxifen or any pharmaceutically acceptable salt thereof. 
     
     
         7 . A pharmaceutical combination according to any one of  claims 1  to  6 , for simultaneous, separate or sequential use in the treatment or prevention of a cancer. 
     
     
         8 - 11 . (canceled) 
     
     
         12 . A method for treating or preventing a cancer in a subject in need thereof comprising administering to said subject a therapeutically effective amount of (a) a phosphatidylinositol-3-kinase (PI3K) inhibitor selected from 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine, (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or any pharmaceutically acceptable salt thereof, (b) a gonadorelin agonist, and, optionally, (c) an antiestrogen agent. 
     
     
         13 . A method according to  claim 12 , wherein pharmaceutical combination comprises (a) a phosphatidylinositol-3-kinase (PI3K) inhibitor selected from 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine, (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or any pharmaceutically acceptable salt thereof, (b) goserelin or any pharmaceutically acceptable salt thereof and (c) tamoxifen or any pharmaceutically acceptable salt thereof. 
     
     
         14 . A method according to  claim 13 , wherein the cancer is hormone-receptor positive breast cancer. 
     
     
         15 . A combined preparation comprising: (a) one or more dosage units of a phosphatidylinositol-3-kinase inhibitor selected from 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine, (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or any pharmaceutically acceptable salt thereof, and (b) one or more dosage units of a gonadorelin agonist for use in the treatment or prevention of a cancer. 
     
     
         16 . A combined preparation according to  claim 15 , further comprising one or more dosage units of an antiestrogen agent. 
     
     
         17 . A commercial package comprising as active ingredients the pharmaceutical combination according to  claim 1  and instructions for simultaneous, separate or sequential administration of said pharmaceutical combination to a patient in need thereof for use in the treatment or prevention of a cancer. 
     
     
         18 . A commercial package comprising as active ingredient a phosphatidylinositol-3-kinase (PI3K) inhibitor according to  claim 1  and instructions for simultaneous, separate or sequential administration of said active ingredient with a gonadorelin agonist to a patient in need thereof for use in the treatment or prevention of a cancer. 
     
     
         19 . The method according to  claim 13 , wherein the cancer is selected from a benign or malignant tumor of the breast, lung, bronchus, prostate, pancreas, colon, rectum, thyroid, liver and intrahepatic bile duct, hepatocellular, gastric, gastrointestine, glioma/glioblastoma, endometrial, melanoma, kidney and renal pelvis, adrenal gland, bladder, uterus, cervix, ovary, esophagus, brain, head and neck, small intestine, multiple myeloma, leukemia, non-Hodgkin lymphoma, villous colon adenoma, a neoplasia, a neoplasia of epithelial character and combinations thereof.