Pharmaceutical combination of MEK inhibitor and B-RAF inhibitors
View Patent ↗A novel combination comprising the MEK inhibitor N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)6,8-dimethyl;-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, with a B-Raf inhibitor, particularly N-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophen-}-2,6-difluorobenzenesulfonamide or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising the same and methods of using such combinations and compositions in the treatment of conditions in which the inhibition of MEK and/or B-Raf is beneficial, eg. cancer.
1. A combination comprising:
(i) a compound of formula (I)
or a pharmaceutically acceptable salt or solvate thereof;
and
(ii) a compound of formula (II)
or a pharmaceutically acceptable salt thereof.
2. A combination according to claim 1 wherein compound (I) is in the form of the dimethylsulfoxide solvate and the compound (II) is in the form of the methanesulfonate salt.
3. A combination kit comprising a combination according to claim 1 together with a pharmaceutically acceptable carrier or carriers.
4. A combination according to claim 1 for use in therapy.
5. A combination according to claim 1 for use in treating cancer.
6. A pharmaceutical composition comprising a combination according to claim 1 together with a pharmaceutically acceptable diluent or carrier.
7. A method of treating melanoma in a human in need thereof which comprises the administration of a therapeutically effective amount of
(i) a compound of formula (I)
or a pharmaceutically acceptable salt or solvate thereof;
and
(ii) a compound of formula (II)
or a pharmaceutically acceptable salt thereof.
8. The method of claim 7 , wherein compound (I) is in the form of the dimethylsulfoxide solvate.
9. The method of claim 7 , wherein the melanoma is metastatic melanoma.
10. The method of claim 7 , wherein compound (II) is in the form of the methanesulfonate salt.
11. The method of claim 7 , wherein the melanoma is BRAF V600E mutant melanoma.
12. A method of treating metastatic melanoma having a BRAT V600E mutation in a human in need thereof which comprises the administration of a therapeutically effective amount of
(i) a compound of formula (I)
or a pharmaceutically acceptable salt car solvate thereof;
and
(ii) a compound of formula (II)
or a pharmaceutically acceptable salt thereof.