Combination therapy for treating malignancies

Patent metadata

Field	Value
Publication number	US-10695352-B2
Application number	US-201615768462-A
Country	US
Kind code	B2
Filing date	Oct 14, 2016
Priority date	Oct 15, 2015
Publication date	Jun 30, 2020
Grant date	Jun 30, 2020

Abstract

Provided are methods and compositions for treating cancers in patients carrying an IDH2 mutation using a combination of an inhibitor of a mutant IDH2 enzyme and a DNA demethylating agent.

First claim

The invention claimed is:

1. A method of treating acute myelogenous leukemia, comprising administering to a subject a mutant isocitrate dehydrogenase 2 (IDH2) inhibitor and azacitidine, wherein the mutant IDH2 inhibitor is 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol having the following formula:

or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer, isotopologue, or a polymorph thereof (Compound 1), and wherein the acute myelogenous leukemia is characterized by the presence of a mutant allele of IDH2.

2. The method of claim 1 , wherein the IDH2 mutation is an IDH2 R140Q or R172K mutation.

3. The method of claim 1 , wherein the acute myelogenous leukemia is newly diagnosed.

4. The method of claim 1 , wherein about 20 to 2000 mg/day of Compound 1 is administered to the subject.

5. The method of claim 1 , wherein about 50 to 500 mg/day of Compound 1 is administered to the subject.

6. The method of claim 1 , wherein about 50 mg/day of Compound 1 is administered to the subject.

7. The method of claim 1 , wherein about 100 mg/day of Compound 1 is administered to the subject.

8. The method of claim 1 , wherein about 200 mg/day of Compound 1 is administered to the subject.

9. The method of claim 1 , wherein about 50 to about 500 mg/m 2 of azacitidine is administered to the subject.

10. The method of claim 1 , wherein about 50 to about 200 mg/m 2 of azacitidine is administered to the subject.

11. The method of claim 1 , wherein about 50 mg/m 2 of azacitidine is administered to the subject.

12. The method of claim 1 , wherein about 60 mg/m 2 of azacitidine is administered to the subject.

13. The method of claim 1 , wherein about 75 mg/m 2 of azacitidine is administered to the subject.

14. The method of claim 1 , wherein Compound 1 and azacitidine are administered concurrently.

15. The method of claim 1 , wherein Compound 1 and azacitidine are administered sequentially.

Assignees

• Celgene Corp
• Agios Pharmaceuticals Inc

Inventors

• Chopra Vivek Saroj Kumar
• Dimartino Jorge
• Kenvin Laurie A
• Knight Robert Douglas
• Macbeth Kyle
• Viswanadhan Krishnan
• Xu Qiang
• Agresta Samuel V

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/7068

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title