Pharmaceutical combinations comprising a B-RAF inhibitor, and EGFR inhibitor and optionally a PI3K-α inhibitor

Patent metadata

Field	Value
Publication number	US-9474754-B2
Application number	US-201314419256-A
Country	US
Kind code	B2
Filing date	Aug 5, 2013
Priority date	Aug 7, 2012
Publication date	Oct 25, 2016
Grant date	Oct 25, 2016

Abstract

A pharmaceutical combination comprising (a) a B-Raf inhibitor, (b) a EGFR inhibitor and, optionally, (c) a PI3K inhibitor; the uses of such combination in the treatment of proliferative diseases; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.

First claim

The invention claimed is:

1. A pharmaceutical combination comprising:
(a) a B-Raf inhibitor of the formula

or a pharmaceutically acceptable salt thereof, and
(b) an EGFR inhibitor, wherein the EGFR inhibitor is erlotinib or cetuximab, and, optionally,
(c) a PI3K-α inhibitor, wherein the PI3K-α inhibitor is Compound B

wherein the B-Raf inhibitor, the EGFR inhibitor, and Compound B are each formulated as single formulations for simultaneous, separate or sequential administration.

2. The pharmaceutical combination of claim 1 wherein the EGFR inhibitor is erlotinib.

3. The pharmaceutical combination of claim 1 wherein the EGFR inhibitor is cetuximab.

4. A method for treating a proliferative disease in a human patient wherein the proliferative disease is characterized by a B-Raf mutation, comprising the simultaneous, separate or sequential administration of a therapeutically effective amount of
(a) a B-Raf inhibitor of the formula

or a pharmaceutically acceptable salt thereof, and
(b) an EGFR inhibitor, wherein the EGFR inhibitor is erlotinib or cetuximab, and, optionally,
(c) a PI3K-α inhibitor, wherein the PI3K-α inhibitor is Compound B

wherein the B-Raf inhibitor, the EGFR inhibitor, and Compound B are each formulated as single formulations.

5. The method according to claim 4 wherein the B-Raf mutation is a V600 mutation.

6. The method according to claim 4 , wherein the proliferative disease is colorectal cancer.

7. The method according to claim 4 , wherein the B-Raf inhibitor is administered orally in an amount of 10 mg per day to 1000 mg per day.

8. The method according to claim 4 , wherein the B-Raf inhibitor is administered orally in an amount of 50 mg per day to 450 mg per day.

9. The method according to claim 7 , wherein the B-Raf inhibitor is administered once or twice per day.

10. The method according to claim 4 , wherein the EGFR inhibitor is cetuximab, wherein the cetuximab is administered as an intravenous infusion in an amount of 200 mg/m 2 to 400 mg/m 2 followed by weekly doses of from 125 mg/m 2 to 250 mg/m 2 .

11. The method according to claim 4 , wherein Compound B is administered orally in an amount of 30 mg per day to 450 mg per day.

12. The method according to claim 11 , wherein Compound B is administered once or twice per day.

13. The method according to claim 4 , wherein the B-Raf inhibitor and cetuximab are administered separately.

14. The method according to claim 4 , wherein the B-Raf inhibitor and Compound B are administered simultaneously.

15. The method according to claim 5 , wherein the V600 mutation is a V600E mutation or a V600K mutation.

16. The method according to claim 6 , wherein the colorectal cancer is characterized by a V600E mutation or a V600K mutation.

Assignees

• Caponigro Giordano
• Stuart Darrin
• Moutouh-De Parseval Laure
• Novartis Ag

Inventors

• Caponigro Giordano
• Stuart Darrin
• Moutouh-De Parseval Laure

Classifications

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title

• A61K31/506 Primary

  not condensed and containing further heterocyclic rings · CPC title

• A61K31/517

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title