Combination therapy for proliferative disorders

Patent metadata

Field	Value
Publication number	US-9486445-B2
Application number	US-201514806427-A
Country	US
Kind code	B2
Filing date	Jul 22, 2015
Priority date	Mar 19, 2012
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

Treatment of proliferative diseases with a combination of a b-Raf inhibitor and MDM2 inhibitor.

First claim

The invention claimed is:

1. A method of treating a patient suffering from cancer, comprising administering to the patient, either concomitantly or sequentially: (i) a first component comprising vemurafenib or a pharmaceutically-acceptable salt thereof, and (ii) a second component comprising Compound II:

or Compound III:

or a pharmaceutically-acceptable salt thereof;
the amount of the first and second components being such that the combination thereof is therapeutically effective in the treatment of said cancer;
wherein the cancer is sarcoma, thyroid cancer, or leukemia, and comprises b-Raf having the V600E mutation.

2. The method of claim 1 wherein said cancer is selected from the group consisting of sarcoma and thyroid cancer.

3. The method of claim 1 wherein said cancer is leukemia.

4. The method of claim 1 wherein the patient is a human patient and vemurafenib, or a pharmaceutically-acceptable salt thereof, is administered in an amount of from about 200 mg/day to about 3000 mg/day.

5. The method of claim 4 wherein vemurafenib, or a pharmaceutically-acceptable salt thereof, is administered in an amount of from about 960 mg/day to about 2000 mg/day.

6. The method of claim 1 wherein the patient is a human patient, and the second component comprises Compound II, or a pharmaceutically-acceptable salt thereof, which is administered in an amount of from about 100 mg/day to about 4500 mg/day.

7. The method of claim 6 wherein Compound II, or a pharmaceutically-acceptable salt thereof, is administered in an amount of from about 500 mg/day to about 3500 mg/day.

8. The method of claim 1 wherein the patient is a human patient and the second component comprises Compound III, or a pharmaceutically-acceptable salt thereof, which is administered in an amount of from about 100 mg/day to about 2500 mg/day.

9. The method of claim 8 wherein Compound III, or pharmaceutically-acceptable salt thereof, is administered in an amount of from about 300 mg/day to about 2000 mg/day.

10. The method of claim 6 wherein vemurafenib, or a pharmaceutically-acceptable salt thereof, is administered in an amount from about 480 mg to about 960 mg bid daily on about day 1 through about day 28 of a 28 day cycle, and Compound II, or a pharmaceutically-acceptable salt thereof, is administered once daily in an amount of about 3500 mg/day for about for up to about 5 days on days 1-5 of a 28 day cycle.

11. The method of claim 6 wherein vemurafenib, or a pharmaceutically-acceptable salt thereof, is administered in an amount from about 480 mg to about 960 mg bid daily on about day 1 through about day 28 of a 28 day cycle, and Compound II, or a pharmaceutically-acceptable salt thereof, is administered in an amount about 1500 mg BID for up to about 10 days on days 1-10 of a 28 day cycle.

12. The method of claim 6 wherein vemurafenib, or a pharmaceutically-acceptable salt thereof, is administered in an amount from about 480 mg to about 960 mg bid daily on about day 1 through about day 28 of a 28 day cycle, and Compound II, or a pharmaceutically-acceptable salt thereof, is administered in an amount of about 4500 mg/day on days 1, 8 and 15 of a 28 day cycle.

13. The method of claim 8 , wherein vemurafenib, or a pharmaceutically-acceptable salt thereof, is administered in an amount from about 480 mg to about 960 mg bid daily on about day 1 through about day 28 of a 28 day cycle, and Compound III, or a pharmaceutically-acceptable salt thereof, is administered once daily in an amount from 300 mg/day to about 2000 mg/day for about for up to about 5 days on days 1-5 of a 28 day cycle.

14. The method of claim 8 , wherein vemurafenib, or a pharmaceutically-acceptable salt thereof, is administered in an amount from about 480 mg to about 960 mg bid daily from about day 1 through about day 28 of a 28 day cycle, and Compound III, or a pharmaceutically-acceptable salt thereof, is administered once weekly in an amount of about 2500 mg/day on days 1, 8 and 15 of a 28 day cycle.

15. The method of claim 1 , wherein the cancer is resistant to vemurafenib prior to administration of the first and second components.

Assignees

• Hoffmann La Roche

Inventors

• Higgins Brian
• Kolinsky Kenneth
• Nichols Gwen
• Packman Kathryn
• Su Fei

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• A61K31/401

  Proline; Derivatives thereof, e.g. captopril · CPC title

• A61K31/437 Primary

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title

• A61K31/40

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title