Method for treating cancer

A method of treating an advanced solid tumor, B cell lymphoma, or a cancer with aberrant H3-K27 methylation, comprising administering orally to a subject in need thereof a dosage form with a therapeutically effective amount of EPZ-6438, wherein said therapeutically effective amount is a single dose to provide a mean AUC(0-12) bioequivalent to a mean AUC(0-12) of from about 4 ng*hr/ml to about 12 ng*hr/ml for each 1 mg of EPZ-6438.

A method of treating an advanced solid tumor, B cell lymphoma, or a cancer with aberrant H3-K27 methylation, comprising administering orally to a subject in need thereof a dosage form with a therapeutically effective amount of EPZ-6438, wherein said therapeutically effective amount provides a mean Cmax bioequivalent to a mean Cmax of from about 102 ng/ml to about 4125 ng/ml.

A method of treating an advanced solid tumor, B cell lymphoma, or a cancer with aberrant H3-K27 methylation, comprising administering orally to a subject in need thereof a dosage form with a therapeutically effective amount of EPZ-6438, wherein said therapeutically effective amount is a single dose to provide a mean Cmax bioequivalent to a mean Cmax of from about 1.2 ng/ml to about 2.6 ng/ml for each 1 mg of EPZ-6438.

A method of treating a solid tumor, B cell lymphoma, or a cancer with aberrant H3-K27 methylation, comprising administering orally to a subject in need thereof a dosage form with a therapeutically effective amount of EPZ-6438, wherein said therapeutically effective amount provides a median Tmax of from about 1 hour to about 2 hours.

The method of any of preceding claims, wherein said administering comprises administering orally a dosage form to the subject, twice per day or three times per day.

A method of inhibiting histone methyltransferase activity of EZH2 or a mutant thereof, comprising administering orally to a subject in need thereof a dosage form with a therapeutically effective amount of EPZ-6438, wherein said therapeutically effective amount provides a mean AUC(0-12) of at least about 4421 ng*hr/ml after administration to the subject.

The method of inhibiting histone methyltransferase activity of EZH2 or a mutant thereof, comprising administering orally to a subject in need thereof a dosage form with a therapeutically effective amount of EPZ-6438, wherein said therapeutically effective amount is a single dose to provide a mean AUC(0-12) bioequivalent to a mean AUC(0-12) of from about 1720 ng*hr/ml to about 18882 ng*hr/ml after administration to the subject.

The method of inhibiting histone methyltransferase activity of EZH2 or a mutant thereof, comprising administering orally to a subject in need thereof a dosage form with a therapeutically effective amount of EPZ-6438, wherein said therapeutically effective amount is a single dose to provide a mean AUC(0-12) bioequivalent to a mean AUC(0-12) of from about 4 ng*hr/ml to about 12 ng*hr/ml for each 1 mg of EPZ-6438.

The method of inhibiting histone methyltransferase activity of EZH2 or a mutant thereof, comprising administering orally to a subject in need thereof a dosage form with a therapeutically effective amount of EPZ-6438, wherein said single dose provides a mean Cmax bioequivalent to a mean Cmax of from about 102 ng/ml to about 4125 ng/ml.

The method of inhibiting histone methyltransferase activity of EZH2 or a mutant thereof, comprising administering orally to a subject in need thereof a dosage form with a therapeutically effective amount of EPZ-6438, wherein said therapeutically effective amount is a single dose to provide a mean Cmax bioequivalent to a mean Cmax of from about 1.2 ng/ml to about 2.6 ng/ml for each 1 mg of EPZ-6438.

The method of claim 31, comprising administering orally to a subject in need thereof a dosage form with a therapeutically effective amount of EPZ-6438, wherein said therapeutically effective amount is a single 800 mg dose, wherein said single dose provides a mean Cmax bioequivalent to a mean Cmax of from about 1730 ng/ml to about 2063 ng/ml.

The method of inhibiting histone methyltransferase activity of EZH2 or a mutant thereof, comprising administering orally to a subject in need thereof a dosage form with a therapeutically effective amount of EPZ-6438, wherein said therapeutically effective amount provides a median Tmax of from about 1 hour to about 2 hours.

An oral dosage form for treating a solid tumor, B cell lymphoma, or a cancer with aberrant H3-K27 methylation, comprising a therapeutically effective amount of EPZ-6438, and at least one pharmaceutically acceptable carrier or excipient, wherein said therapeutically effective amount is a single dose to provide a mean AUC(0-12) bioequivalent to a mean AUC(0-12) of from about 102 ng*hr/ml to about 18882 ng*hr/ml after administration to a human subject.

An oral dosage form for treating an advanced solid tumor or B cell lymphoma, comprising a therapeutically effective amount of EPZ-6438, and at least one pharmaceutically acceptable carrier or excipient, wherein said therapeutically effective amount is a single dose to provide a mean AUC(0-12) bioequivalent to a mean AUC(0-12) of from about 4 ng*hr/ml to about 12 ng*hr/ml for each 1 mg of EPZ-6438.

The dosage form for treating an advanced solid tumor or B cell lymphoma, comprising a therapeutically effective amount of EPZ-6438, and at least one pharmaceutically acceptable carrier or excipient, wherein said therapeutically effective amount provides a mean Cmax bioequivalent to a mean Cmax of from about 102 ng/ml to about 4125 ng/ml.

The dosage form for treating an advanced solid tumor or B cell lymphoma, comprising a therapeutically effective amount of EPZ-6438, and at least one pharmaceutically acceptable carrier or excipient, wherein said therapeutically effective amount is a single dose to provides a mean Cmax bioequivalent to a mean Cmax of from about 1.2 ng/ml to about 2.6 ng/ml for each 1 mg of EPZ-6438.

An oral dosage form for treating an advanced solid tumor or B cell lymphoma, comprising a therapeutically effective amount of EPZ-6438, and at least one pharmaceutically acceptable carrier or excipient, wherein said therapeutically effective amount provides a mean AUC(0-12) of at least about 4421 ng*hr/ml after administration to a human subject.

A method of treating an advanced solid tumor or B cell lymphoma, comprising administering orally to a subject in need thereof a dosage form with a therapeutically effective amount of EPZ-643 8, wherein said therapeutically effective amount provides a mean AUC(0-12) of at least about 4421 ng*hr/ml after administration to the subject.

The method or oral dosage form of any preceding claims, wherein the therapeutically effective amount is a single 100 mg, 200 mg, 400 mg, 800 mg, or 1600 mg dose.

A solid pharmaceutical formulation comprising a therapeutic agent and one or more pharmaceutically acceptable excipients, wherein the therapeutic agent is N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl) amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide:

• or its salt, or a combination thereof, and wherein the one or more pharmaceutically acceptable excipients are selected from sodium starch glycolate, carmellose, carmellose calcium, croscarmellose sodium, low-substituted hydroxypropylcellulose, and a combination thereof.