Combination therapy for treating malignancies
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.
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.