Methods of treatment of malignancies
Provided are methods and compositions for treating cancers in patients carrying an IDH1 mutation or IDH2 mutation.
1. A method of treating acute myeloid leukemia in a subject comprising administering to the subject a mutant isocitrate dehydrogenase 2 (IDH2) inhibitor 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, or tautomer thereof, wherein the acute myeloid leukemia is characterized by the presence of a mutant allele of IDH2 and the absence of a mutant allele of NRAS.
2. The method of claim 1 , wherein the mutant allele of IDH2 is IDH2 R140Q or R172K.
3. The method of claim 1 , wherein the acute myelogenous leukemia is relapsed or refractory acute myelogenous leukemia, characterized by the presence of a mutant allele of IDH2.
4. The method of claim 1 , wherein 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 or a pharmaceutically acceptable salt, solvate or tautomer thereof is administered in a dose of about 20 to 2000 mg/day.
5. The method of claim 4 , wherein 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 or a pharmaceutically acceptable salt, solvate or tautomer thereof is administered in a dose of about 50 to 500 mg/day.
6. The method of claim 1 , wherein the subject has 3 or less co-occuring mutations.
7. The method of claim 1 , wherein the mutant isocitrate dehydrogenase 2 (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.
8. The method of claim 1 , wherein the mutant isocitrate dehydrogenase 2 (IDH2) inhibitor is a mesylate salt of 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.