Pharmaceutical combinations of a CDK4/6 inhibitor and a B-RAF inhibitor

Patent metadata

Field	Value
Publication number	US-9700557-B2
Application number	US-201314414998-A
Country	US
Kind code	B2
Filing date	Jul 25, 2013
Priority date	Jul 26, 2012
Publication date	Jul 11, 2017
Grant date	Jul 11, 2017

Abstract

A pharmaceutical combination comprising (a) CDK4/6 inhibitor (b) a B-Raf inhibitor, and optionally (c) a MEK 1/2 inhibitor; combined preparations and pharmaceutical compositions thereof; 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 CDK4/6 inhibitor of the formula

or a pharmaceutically acceptable salt thereof, and
(b) a B-Raf inhibitor of the formula

or a pharmaceutically acceptable salt thereof,

for simultaneous, separate or sequential administration.

2. The pharmaceutical combination according to claim 1 which further comprises a MEK 1/2 inhibitor.

3. The pharmaceutical combination according to claim 2 wherein the MEK 1/2 inhibitor is a compound of the formula

or a pharmaceutically acceptable salt thereof.

4. A method for treating a proliferative disease in a human patient, comprising simultaneously, separately or sequentially administering to the patient a therapeutically effective amount of
(a) a CDK4/6 inhibitor of the formula

or a pharmaceutically acceptable salt thereof, and
(b) a B-Raf inhibitor of the formula

or a pharmaceutically acceptable salt thereof.

5. The method according to claim 4 , wherein the proliferative disease is melanoma, lung cancer, colorectal cancer (CRC), breast cancer, kidney cancer, renal cell carcinoma (RCC), liver cancer, acute myelogenous leukemia (AML), myelodysplastic syndromes (MDS), non-small-cell lung cancer (NSCLC), thyroid cancer, pancreatic cancer, neurofibromatosis or hepatocellular carcinoma.

6. The method according to claim 5 , wherein the proliferative disease is characterized by a B-Raf mutation.

7. The method according to claim 5 , wherein the proliferative disease is characterized by a B-Raf V600 mutation.

8. The method according to claim 7 , wherein the proliferative disease is melanoma or colorectal cancer.

9. A combined preparation which comprises the pharmaceutical combination according to claim 1 .

10. A pharmaceutical composition which comprises the pharmaceutical combination according to claim 1 .

11. The method according to claim 7 , wherein the B-Raf V600 mutation is a V600E mutation, a V600K mutation, or a V600G mutation.

12. The method according to claim 4 , wherein the method further comprises simultaneously, separately or sequentially administering to the patient a therapeutically effective amount of a MEK 1/2 inhibitor.

13. The method according to claim 12 , wherein the MEK 1/2 inhibitor is a compound of the formula

or a pharmaceutically acceptable salt thereof.

Assignees

• Novartis Ag

Inventors

• Caponigro Giordano
• Stuart Darrin
• Kim Sunkyu
• Loo Alice
• Delach Scott

Classifications

• A61P5/14

  of the thyroid hormones, e.g. T3, T4 · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title