Therapeutically active compounds and their methods of use
Provided are compounds useful for treating cancer and methods of treating cancer, for example an advanced solid tumor, such as a glioma, or angioimmunoblastic T-cell lymphoma (AITL).
1. A method of treating a solid tumor characterized by the presence of a mutant allele of isocitrate dehydrogenase 2 (IDH2) comprising administering to a subject in need thereof a therapeutically effective dose of an inhibitor of a mutant IDH2, wherein the 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 or 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 methanesulfonate, wherein the therapeutically effective dose is from about 30 mg to about 300 mg.
2. The method of claim 1 , wherein the solid tumor is glioma, melanoma, chondrosarcoma, or cholangiocarcinoma.
3. A method of treating angioimmunoblastic T-cell lymphoma (AITL) characterized by the presence of a mutant allele of isocitrate dehydrogenase 2 (IDH2) comprising administering to a subject in need thereof a therapeutically effective dose of an inhibitor of a mutant IDH2, wherein the 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 or 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 methanesulfonate, wherein the therapeutically effective dose is from about 30 mg to about 300 mg.
4. The method of claim 1 , wherein the 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 or a crystalline form thereof.
5. The method of claim 1 , wherein the 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 methanesulfonate or a crystalline form thereof.
6. The method of claim 3 , wherein the 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 or a crystalline form thereof.
7. The method of claim 3 , wherein the 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 methanesulfonate or a crystalline form thereof.
8. 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 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 methanesulfonate is administered orally.
9. The method of claim 1 , wherein the therapeutically effective dose is from about 30 mg to about 200 mg.
10. The method of claim 9 , wherein the therapeutically effective dose is from about 30 mg to about 150 mg.
11. The method of claim 1 , wherein the therapeutically effective dose is about 30 mg, or about 50 mg, or about 75 mg, or about 100 mg, or about 125 mg, or about 150 mg, or about 175 mg, or about 200 mg, or about 225 mg, or about 250 mg or about 275 mg, or about 300 mg.
12. The method of claim 8 , wherein the 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 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 methanesulfonate is administered in a 50 mg, a 100 mg, a 150 mg, or a 200 mg oral dosage form.
13. The method of claim 3 , 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 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 methanesulfonate is administered orally.
14. The method of claim 13 , wherein the therapeutically effective dose is from about 30 mg to about 200 mg.
15. The method of claim 14 , wherein the therapeutically effective dose is from about 30 mg to about 150 mg.
16. The method of claim 13 , wherein the therapeutically effective dose is about 30 mg, or about 50 mg, or about 75 mg, or about 100 mg, or about 125 mg, or about 150 mg, or about 175 mg, or about 200 mg, or about 225 mg, or about 250 mg or about 275 mg, or about 300 mg.
17. The method of claim 13 , wherein the 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 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 methanesulfonate is administered in a 50 mg, a 100 mg, a 150 mg, or a 200 mg oral dosage form.