USE OF INHIBITORS OF BRUTON'S TYROSINE KINASE (BTK)
Disclosed herein are methods for treating a cancer comprising: a. administering a Btk inhibitor to a subject sufficient to result in an increase or appearance in the blood of a subpopulation of lymphocytes defined by immunophenotyping; b. determining the expression profile of one or more biomarkers from one or more subpopulation of lymphocytes; and c. administering a second agent based on the determined expression profile.
1 .- 129 . (canceled)
130 . A pharmaceutical composition comprising about 140 mg of a Bruton's tyrosine kinase (BTK) inhibitor compound of Formula (D):
wherein
La is CH2, O, NH or S;
Ar is a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl;
Y is an optionally substituted group selected from among alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
Z is C(═O), OC(═O), NHC(═O), C(═S), S(═O)x, OS(═O)x, NHS(═O)x, where x is 1 or 2;
R7 and R8 are independently H; or
R7 and R8 taken together form a bond;
R6 is H,
and a pharmaceutically-acceptable excipient.
131 . The pharmaceutical composition of claim 130 , wherein the dosage form is an oral dosage form.
132 . The pharmaceutical composition of claim 130 , wherein the dosage form is a tablet, a pill, a powder, a capsule, a solid dispersion, a solid solution, a bioerodible dosage form, a controlled release formulation, a pulsatile release dosage form, a multiparticulate dosage form, a pellet, a granule, or an aerosol.
133 . The pharmaceutical composition of claim 130 , wherein the dosage form is a capsule.
134 . The pharmaceutical composition of claim 130 , wherein the dosage form is a tablet.
135 . The pharmaceutical composition of claim 130 , wherein the dosage form is a pill.
136 . The pharmaceutical composition of claim 130 , wherein the compound of Formula (D) is (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one (ibrutinib).
137 . The pharmaceutical composition of claim 136 , wherein the dosage form is an oral dosage form.
138 . The pharmaceutical composition of claim 136 , wherein the dosage form is a tablet, a pill, a powder, a capsule, a solid dispersion, a solid solution, a bioerodible dosage form, a controlled release formulation, a pulsatile release dosage form, a multiparticulate dosage form, a pellet, a granule, or an aerosol.
139 . The pharmaceutical composition of claim 136 , wherein the dosage form is a capsule.
140 . The pharmaceutical composition of claim 136 , wherein the dosage form is a tablet.
141 . The pharmaceutical composition of claim 136 , wherein the dosage form is a pill.
142 . A pharmaceutical composition comprising about 140 mg of (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one (ibrutinib), and a pharmaceutically-acceptable excipient, formulated into a solid dosage form.