Pharmaceutical compositions of therapeutically active compounds
Provided are compounds and pharmaceutical compositions useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound or pharmaceutical composition described herein.
1. A pharmaceutical composition comprising: (a) a solid dispersion comprising between about 25-75% w/w of (S)—N—((S)-1-(2-chlorophenyl)-2-((3,3-difluorocyclobutyl)amino)-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide (Compound 1), or a pharmaceutically acceptable salt thereof, and between about 25-75% w/w of a polyvinylpyrrolidone-vinyl acetate (PVP-VA) copolymer; and optionally (b) one or more pharmaceutically acceptable carrier(s).
2. The pharmaceutical composition of claim 1 wherein the PVP-VA polymer is copovidone.
3. The pharmaceutical composition of claim 1 or 2 wherein the solid dispersion is a spray-dried dispersion.
4. The pharmaceutical composition of claim 1 or 2 wherein the solid dispersion is a spray-dried dispersion.
5. The pharmaceutical composition of claim 1 or 2 wherein the solid dispersion comprises between about 30 and 70% w/w Compound 1.
6. The pharmaceutical composition of claim 1 or 2 wherein the solid dispersion comprises between about 40 and 60% compound 1.
7. The pharmaceutical composition of claim 1 or 2 wherein the solid dispersion comprises about 50% w/w Compound 1.
8. The pharmaceutical composition of claim 1 or 2 wherein the solid dispersion comprises about 25% Compound 1.
9. The pharmaceutical composition of claim 1 or 2 wherein the solid dispersion comprises about 75% Compound I.
10. The pharmaceutical composition of claim 1 or 2 wherein the dispersion is an amorphous dispersion.
11. A pharmaceutical composition for oral administration comprising (a) a solid dispersion comprising about 50% w/w of (S)—N—((S)-1-(2-chlorophenyl)-2-(3,3-difluorocyclobutyl)amino)-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide (Compound 1) or a pharmaceutically acceptable salt thereof and about 50% w/w of copovidone and optionally (b) one or more pharmaceutically acceptable carrier(s).
12. The pharmaceutical composition of claim 11 wherein the pharmaceutical composition is a tablet.
13. A method of treating acute myelogenous leukemia (AML) in a subject, characterized by the presence of a mutant allele of IDH1, the method comprising administering to the subject in need thereof a pharmaceutical composition comprising (a) a solid dispersion comprising between about 25-75% w/w of (S)—N—((S)-1-(2-chlorophenyl)-2-(3,3-difluorocyclobutyl)amino)-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide (Compound 1) or a pharmaceutically acceptable salt thereof, and between about 25-75% w/w of a polyvinylpyrrolidone-vinyl acetate (PVP-VA) copolymer and optionally (b) one or more pharmaceutically acceptable carrier(s).
14. The method of claim 13 wherein the pharmaceutical composition comprises (a) a solid dispersion comprising about 50% w/w of (S)—N—((S)-1-(2-chlorophenyl)-2-(3,3-difluorocyclobutyl)amino)-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide (Compound 1) or a pharmaceutically acceptable salt thereof, and about 50% w/w of copovidone and optionally (b) one or more pharmaceutically acceptable carrier(s).
15. The method of claim 13 or 14 , wherein the mutant IDH1 has an R132X mutation.
16. The method of claim 15 , wherein the R132X mutation is selected from R132H, R132C, R132L, R132V, R132S and R132G.
17. The method of claim 16 , wherein the R132X mutation is R132H or R132C.