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 for oral administration comprising (a) a solid dispersion comprising between 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 a cellulosic polymer and optionally (b) one or more pharmaceutically acceptable carrier(s).
2. The pharmaceutical composition of claim 1 wherein the polymer is selected from selected from hydroxypropylmethylcelulose acetate succinate (HPMCAS) and hydroxypropylmethylcellulose (HPMC).
3. The pharmaceutical composition of claim 1 wherein the solid dispersion is a spray-dried dispersion.
4. The pharmaceutical composition of claim 1 wherein the solid dispersion comprises between about 30 and 70% w/w Compound 1.
5. The pharmaceutical composition of claim 4 wherein the solid dispersion comprises between about 40 and 60% compound 1.
6. The pharmaceutical composition of claim 5 wherein the solid dispersion comprises about 50% w/w Compound 1.
7. 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 hydroxypropylmethylcelulose acetate succinate (HPMCAS) and optionally (b) one or more pharmaceutically acceptable carrier(s).
8. 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 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 a cellulosic polymer selected from hydroxypropylmethylcelulose acetate succinate (HPMCAS) and hydroxypropylmethylcellulose (HPMC) and optionally (b) one or more pharmaceutically acceptable carrier(s).
9. 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 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 hydroxypropylmethylcelulose acetate succinate (HPMCAS) and optionally (b) one or more pharmaceutically acceptable carrier(s).
10. The method of claim 9 , wherein the mutant IDH1 has an R132X mutation.
11. The method of claim 10 , wherein the R132X mutation is selected from R132H, R132C, R132L, R132V, R132S and R132G.
12. The method of claim 11 , wherein the R132X mutation is R132H or R132C.