Combination therapy for proliferative disorders

Patent metadata

Field	Value
Publication number	US-9295669-B2
Application number	US-201113313042-A
Country	US
Kind code	B2
Filing date	Dec 7, 2011
Priority date	Dec 14, 2010
Publication date	Mar 29, 2016
Grant date	Mar 29, 2016

Abstract

The present invention relates to a combination therapy of propane-1-sulfonic acid{3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl-2,4-difluoro-phenyl]-amide}, or a pharmaceutically acceptable salt thereof, and an interferon for treating a patient suffering from a proliferative disorder, in particular a solid tumor, for example, colorectal cancer, melanoma, and thyroid cancer. In particular, the present invention relates to such a therapy wherein the interferon is peginterferon alfa-2a and the disorder is melanoma containing the V600E b-Raf mutation.

First claim

The invention claimed is:

1. A method of treating a patient suffering from a proliferative disorder, comprising administering to the patient: (A) a first component which comprises, as an active agent, propane-1-sulfonic acid{3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl-2,4-difluoro-phenyl]amide}, or a pharmaceutically acceptable salt thereof; and (B) a second component which comprises, as an active agent, peginterferon alfa-2a;
wherein said propane-1-sulfonic acid{3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl-2,4-difluoro-phenyl]amide} is administered in an amount of from about 1700 mg/day to about 2100 mg/day, wherein said amount is about 25 mg/kg, and
said peginterferon alfa-2a is administered in an amount of from about 180 μg/week to about 630 μg/week, and
wherein said proliferative disorder is selected from the group consisting of: colorectal cancer, melanoma, and thyroid cancer, wherein said cancer involves a tumor comprising b-Raf having the V600E mutation.

2. A method according to claim 1 wherein said patient is a human.

3. A method according to claim 1 wherein said proliferative disorder is melanoma containing the V600E b-Raf mutation.

4. A method according to claim 1 wherein propane-1-sulfonic acid{3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl-2,4-difluoro-phenyl]amide}, or a pharmaceutically acceptable salt thereof, is substantially in amorphous form.

5. A method according to claim 1 wherein propane-1-sulfonic acid{3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl-2,4-difluoro-phenyl]amide}, or a pharmaceutically acceptable salt thereof, is in amorphous form.

6. A method according to claim 1 wherein propane-1-sulfonic acid{3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl-2,4-difluoro-phenyl]amide}, or a pharmaceutically acceptable salt thereof, is contained in a solid molecular complex formed with hydroxypropyl methyl cellulose acetate succinate such that it is immobilized in its amorphous form.

7. A method according to claim 6 wherein the amounts of propane-1-sulfonic acid{3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl-2,4-difluoro-phenyl]amide}, or a pharmaceutically acceptable salt thereof, are hydroxypropyl methyl cellulose acetate succinate in said complex are in a ratio of from about 1:9 to about 5:5, respectively.

8. A method according to claim 6 wherein the amounts of propane-1-sulfonic acid{3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl-2,4-difluoro-phenyl]amide}, or a pharmaceutically acceptable salt thereof, and hydroxypropyl methyl cellulose acetate succinate in said complex are in a ratio of about 3:7, respectively.

9. A method according to claim 6 wherein said first component comprises a blend wherein about 97% by weight of the blend is said complex and about 3% by weight of the blend is silicon dioxide.

10. A method according to claim 6 wherein said first component comprises a suspension of said complex in a pharmaceutically acceptable carrier.

11. A method according to claim 1 wherein said first component comprises a tablet comprising a solid molecular complex of propane-1-sulfonic acid{3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl-2,4-difluoro-phenyl]amide}, or a pharmaceutically acceptable salt thereof, and hydroxypropyl methyl cellulose acetate succinate.

Assignees

• Dhingra Kapil
• Higgins Brian
• Kolinsky Kenneth
• Lee Richard J
• Lestini Brian
• Packman Kathryn
• Su Fei
• Hoffmann La Roche

Inventors

• Dhingra Kapil
• Higgins Brian
• Kolinsky Kenneth
• Lee Richard J
• Lestini Brian
• Packman Kathryn
• Su Fei

Classifications

• A61P43/00

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

• A61P35/00

  Antineoplastic agents · 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

• A61K38/212 Primary

  IFN-alpha · CPC title

• A61K38/21

  Interferons {[IFN]} · CPC title