Spray-dried dispersions, formulations, and polymorphs of (s)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1h-pyrazole-4-carboxamide

A pharmaceutical composition comprising a compound of Formula I:

• or a pharmaceutically acceptable salt thereof;
• a HPMCAS polymer;
• and one or more pharmaceutical excipients.

A pharmaceutical composition in the form of a tablet containing 0.01, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 15.0, 20.0, 25.0, 30.0, 40.0, 50.0, 60.0, 70.0, 75.0, 80.0, 90.0, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, or 500 milligrams of (S)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide.

A pharmaceutical composition comprising (S)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide present in an amount of about 25 mg to about 220 mg.

A method of treating cancer comprising administering a compound of Formula I:

• or a pharmaceutically acceptable salt thereof to a human subject in need of treatment thereof in a dose between about 20 mg and about 120 mg and wherein the cancer is selected from the group consisting of:
• mantle cell lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma, Waldenstrom's macroglobulinemia, and marginal zone lymphoma.

A method of treating a disease or disorder mediated by BTK comprising administering an oral pharmaceutical composition to a human subject in need of treatment thereof containing a dose of a (S)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide in a dosing range of 0.5 mg/kg to 7.5 mg/kg body weight.

A method of treating a BTK-associated cancer selected from the group consisting of mantle cell lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma, Waldenstrom's macroglobulinemia, and marginal zone lymphoma comprising administering a therapeutically effective amount of a compound which is (S)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide or a pharmaceutically acceptable salt thereof, to a human subject in need thereof wherein the compound or salt is in an amorphous form, a spray-dried dispersion, and/or a pharmaceutical composition, in combination with a therapeutically effective amount of at least one additional therapeutic agent.

A crystalline form of a compound which is (S)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide characterized by having an X-ray powder diffraction pattern comprising peaks at ° 2θ values of 15.8±0.2, 16.2±0.2, and 11.9±0.2.