Combination of (a) a phosphoinositide 3-kinase inhibitor and (b) a modulator of RAS/RAF/MEK pathway
The invention relates to a pharmaceutical combination which comprises (a) a phosphoinositide 3-kinase inhibitor compound and (b) a compound which modulates the Ras/Raf/Mek pathway for the treatment of a proliferative disease, especially a solid tumor disease; a pharmaceutical composition comprising such a combination; the use of such a combination for the preparation of a medicament for the treatment of a proliferative disease; a commercial package or product comprising such a combination as a combined preparation for simultaneous, separate or sequential use; and to a method of treatment of a warm-blooded animal, especially a human.
1. A method of treating a warm-blooded animal having a pancreatic cancer, comprising simultaneously, sequentially or separately administering to said animal (a) a phosphoinositide 3-kinase inhibitor compound selected from 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine and (b) a compound which modulates Mek kinase activity selected from ARRY142886/AZD6244, ARRY162, and GSK1120212, wherein the active ingredients are present in free form or in the form of a pharmaceutically acceptable salt thereof, in a quantity which is therapeutically effective against said proliferative disease.
2. A method according to claim 1 , wherein the compound which modulates Mek kinase activity is ARRY162, or GSK1120212 or a pharmaceutically acceptable salt thereof.
3. A method according to claim 1 , wherein the pancreatic cancer has a genetic alteration in the Ras/Raf/Mek signal transduction pathway consisting of a HRAS, KRAS, NRAS or BRAF mutation or gene amplification.
4. A method of treating a warm-blooded animal having a pancreatic cancer, comprising administering to said animal (a) a phosphoinositide 3-kinase inhibitor compound 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine and (b) a compound GSK1120212, wherein the active ingredients are present in free form or in the form of a pharmaceutically acceptable salt thereof, in a quantity which is therapeutically effective against said pancreatic cancer.