Abstract: The present invention relates to methods of treating or preventing a proliferative disease in a patient in need thereof by orally administering a therapeutically effective amount of an alpha-isoform selective phosphatidylinositol 3-kinase inhibitor compound of formula (I) or a pharmaceutically acceptable salt thereof for at least two five-consecutive day cycle, wherein said compound is not administered to the patient for a period of about two days to about three days between said five-consecutive day cycles; the use of said compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating or preventing a proliferative disease administered in accordance with said dosage regimen; therapeutic regimen comprising administration of said compound of formula (I) or a pharmaceutically acceptable salt thereof in accordance with said dosage regimen; and related pharmaceutical compositions and packages thereof.

Abstract: Selective cancer treatment regimes based on assaying for the presence or absence of a mutation in PI3K in a blood or serum sample obtained from a patient having cancer. The cancer is treated with 5-(2,6-di-mor-pholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine or its hydrochloride salt, or (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) on the basis that the patient is determined to have in their ctDNA a PIK3CA mutation.

Abstract: The present invention relates to methods of identifying subjects suffering from various types of cancer who are more likely to respond to treatment with a covalent CDK7 inhibitor, such as N-((1S,3R)-3-(5-chloro-4-(1H-indol-3-yl)pyrimidin-2-ylamino)-1-methylcyclohexyl)-5-((E)-4-(dimethylamino)but-2-enamido)picolinamide (Compound 1), either alone or in combination with other classes of anti-cancer therapies based on the presence or absence of certain biomarkers. In addition, the present invention relates to combinations of Compound 1 and one or more other anti-cancer therapies, kits containing them, and the use of such combinations in treating subjects suffering from various types of cancers.

Abstract: The present invention relates to methods of treating or preventing a proliferative disease in a patient in need thereof by orally administering a therapeutically effective amount of an alpha-isoform selective phosphatidylinositol 3-kinase inhibitor compound of formula (I) or a pharmaceutically acceptable salt thereof for at least two five-consecutive day cycle, wherein said compound is not administered to the patient for a period of about two days to about three days between said five-consecutive day cycles; the use of said compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating or preventing a proliferative disease administered in accordance with said dosage regimen; therapeutic regimen comprising administration of said compound of formula (I) or a pharmaceutically acceptable salt thereof in accordance with said dosage regimen; and related pharmaceutical compositions and packages thereof.

Abstract: The present invention relates to methods of treating or preventing a proliferative disease in a patient in need thereof by orally administering a therapeutically effective amount of an alpha-isoform selective phosphatidylinositol 3-kinase inhibitor compound of formula (I) or a pharmaceutically acceptable salt thereof for at least two five-consecutive day cycle, wherein said compound is not administered to the patient for a period of about two days to about three days between said five-consecutive day cycles; the use of said compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating or preventing a proliferative disease administered in accordance with said dosage regimen; therapeutic regimen comprising administration of said compound of formula (I) or a pharmaceutically acceptable salt thereof in accordance with said dosage regimen; and related pharmaceutical compositions and packages thereof.

Abstract: Selective cancer treatment regimes based on assaying for the presence or absence of a mutation in PI3K in a blood or serum sample obtained from a patient having cancer. The cancer is treated with 5-(2,6-di-mor-pholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine or its hydrochloride salt, or (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) on the basis that the patient is determined to have in their ctDNA a PIK3CA mutation.

Abstract: A method of treating or preventing a proliferative disease in a patient in need thereof by orally administering a therapeutically effective amount of a phosphatidylinositol 3-kinase inhibitor compound or a pharmaceutically acceptable salt thereof once-per-day either on a continuous daily schedule or an intermittent schedule at about zero to about three hours prior to sleep; a therapeutic regimen comprising administration of said compound or a pharmaceutically acceptable salt thereof in accordance with said dosage regimen; and related pharmaceutical compositions and packages thereof.

Abstract: The present invention relates to methods of treating or preventing a proliferative disease in a patient in need thereof by orally administering a therapeutically effective amount of an alpha-isoform selective phosphatidylinositol 3-kinase inhibitor compound of formula (I) or a pharmaceutically acceptable salt thereof for at least two five-consecutive day cycle, wherein said compound is not administered to the patient for a period of about two days to about three days between said five-consecutive day cycles; the use of said compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating or preventing a proliferative disease administered in accordance with said dosage regimen; therapeutic regimen comprising administration of said compound of formula (I) or a pharmaceutically acceptable salt thereof in accordance with said dosage regimen; and related pharmaceutical compositions and packages thereof.

Abstract: A pharmaceutical combination comprising (a) a phosphatidylinositol-3-kinase (PI3K) inhibitor compound of formula (I), as defined herein, or a pharmaceutically acceptable salt thereof and (b) paclitaxel or a pharmaceutically acceptable salt thereof for simultaneous, separate or sequential use, for the treatment of a cancer of the head and neck; a pharmaceutical composition comprising said combination; the use of said combination for the preparation of a medicament for the treatment of a cancer of the head and neck; a method of treating or preventing a cancer of the head and neck comprising administering a jointly therapeutically effective amount of such a combination to a subject in need thereof; and a commercial package thereof.

Abstract: A pharmaceutical combination comprising (a) a phosphatidylinositol-3-kinase (PI3K) inhibitor compound of formula (I), as defined herein, or a pharmaceutically acceptable salt thereof and (b) paclitaxel or a pharmaceutically acceptable salt thereof for simultaneous, separate or sequential use, for the treatment of a cancer of the head and neck; a pharmaceutical composition comprising said combination; the use of said combination for the preparation of a medicament for the treatment of a cancer of the head and neck; a method of treating or preventing a cancer of the head and neck comprising administering a jointly therapeutically effective amount of such a combination to a subject in need thereof; and a commercial package thereof.

Abstract: A pharmaceutical combination comprising (a) the phosphatidylinositol 3-kinase (PI3K) inhibitor compound (S)-pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]thiazol-2-yl}-amide) or a pharmaceutically acceptable salt thereof, and (b) at least one mitogen activated protein kinase (MEK) inhibitor or a pharmaceutically acceptable salt, and optionally at least one pharmaceutically acceptable carrier, for simultaneous, separate or sequential administration; the uses of such combination in the treatment of proliferative diseases; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.

Abstract: The present invention relates to methods of treating or preventing a proliferative disease in a patient in need thereof by orally administering a therapeutically effective amount of an alpha-isoform selective phosphatidylinositol 3-kinase inhibitor compound of formula (I) or a pharmaceutically acceptable salt thereof for at least two five-consecutive day cycle, wherein said compound is not administered to the patient for a period of about two days to about three days between said five-consecutive day cycles; the use of said compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating or preventing a proliferative disease administered in accordance with said dosage regimen; therapeutic regimen comprising administration of said compound of formula (I) or a pharmaceutically acceptable salt thereof in accordance with said dosage regimen; and related pharmaceutical compositions and packages thereof.

Abstract: A pharmaceutical combination comprising: (a) a phosphatidylinositol-3-kinase inhibitor selected from 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile, 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine, (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or any pharmaceutically acceptable salt thereof, and (b) an anaplastic lymphoma kinase inhibitor, particularly for use in the treatment or prevention of a proliferative disease; uses of such a combination in the treatment or prevention of proliferative diseases; to pharmaceutical compositions of the combination of said therapeutic agents and methods of treating a proliferative disease in a subject comprising administering to said subject a therapeutically effective amount of such a combination.

Abstract: A pharmaceutical combination comprising (a) a phosphatidylinositol-3-kinase (PI3K) inhibitor compound of formula (I), as defined herein, or a pharmaceutically acceptable salt thereof and (b) paclitaxel or a pharmaceutically acceptable salt thereof for simultaneous, separate or sequential use, for the treatment of a cancer of the head and neck; a pharmaceutical composition comprising said combination; the use of said combination for the preparation of a medicament for the treatment of a cancer of the head and neck; a method of treating or preventing a cancer of the head and neck comprising administering a jointly therapeutically effective amount of such a combination to a subject in need thereof; and a commercial package thereof.

Abstract: A pharmaceutical combination comprising (a) the phosphatidylinositol 3-kinase (PI3K) inhibitor compound (S)-pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or a pharmaceutically acceptable salt thereof, and (b) at least one mitogen activated protein kinase (MEK) inhibitor or a pharmaceutically acceptable salt, and optionally at least one pharmaceutically acceptable carrier, for simultaneous, separate or sequential administration; the uses of such combination in the treatment of proliferative diseases; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.