Abstract: The present invention relates to a pharmaceutical combination which comprises (a) a phosphatidylinositol 3-kinase inhibitor or pharmaceutically acceptable salt thereof, and (b) at least one c-Met receptor tyrosine kinase inhibitor or pharmaceutically acceptable salt thereof, for simultaneous, separate or sequential administration for the treatment of a proliferative disease, particularly a c-Met dependent proliferative disease; a pharmaceutical composition comprising such combination; a method of treating a subject having a proliferative disease comprising administration of said combination to a subject in need thereof; use of such combination for the treatment of proliferative disease; and a commercial package comprising such combination.

Abstract: The present disclosure pertains to a pharmaceutical combination comprising (a) an alpha-isoform specific PI3K inhibitor, (b) a cyclin dependent kinase 4/6 (CDK4/6) inhibitor, and (c) an antimetabolite antineoplastic agent; combined preparations and pharmaceutical compositions thereof; the uses of such a combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject comprising administering a therapeutically effective amount of such combination.

Abstract: The present disclosure relates to a pharmaceutical combination comprising (a) alpha-isoform specific PI3K inhibitor and (b) a B-RAF inhibitor; combined preparations and pharmaceutical compositions thereof; the uses of such combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject comprising administering a therapeutically effective amount of such combination.

Abstract: The present invention relates to the use of a c-Raf inhibitor for use in the treatment of a proliferative disease, particularly a solid tumor that harbors Mitogen-activated protein kinase (MAPK). The present invention also relates to a pharmaceutical combination which comprises (a) at least one antibody molecule (e.g., humanized antibody molecules) that binds to Programmed Death 1 (PD-1), and (b) a c-Raf inhibitor or pharmaceutically acceptable salt thereof. The present invention also relates to such a combination for simultaneous, separate or sequential administration for the treatment of a proliferative disease, particularly a solid tumor that harbors Mitogen-activated protein kinase (MAPK) alteration and a commercial package comprising such a combination.

Abstract: Provided herein are pharmaceutical combinations comprising (a) a B-Raf inhibitor, or a pharmaceutically acceptable salt thereof, (b) at least one mitogen activated protein kinase (MEK) inhibitor, or a pharmaceutically acceptable salt thereof, and (c) an epidermal growth factor receptor (EGFR) inhibitor or a pharmaceutically acceptable salt thereof; and optionally at least one pharmaceutically acceptable carrier; methods for preparing the pharmaceutical combinations, and the uses of the pharmaceutical combinations in the treatment of proliferative diseases, such as cancer.

Abstract: The present invention relates to a pharmaceutical combination which comprises (a) a phosphatidylinositol 3-kinase inhibitor or pharmaceutically acceptable salt thereof, and (b) at least one c-Met receptor tyrosine kinase inhibitor or pharmaceutically acceptable salt thereof, for simultaneous, separate or sequential administration for the treatment of a proliferative disease, particularly a c-Met dependent proliferative disease; a pharmaceutical composition comprising such combination; a method of treating a subject having a proliferative disease comprising administration of said combination to a subject in need thereof; use of such combination for the treatment of proliferative disease; and a commercial package comprising such combination.

Abstract: The present disclosure relates to a pharmaceutical combination comprising (a) an Mdm2 inhibitor and (b)(i) a MEK inhibitor and/or (b)(ii) Bcl2 inhibitor, particularly for use in the treatment of a cancer. This disclosure also relates to uses of such combination for preparation of a medicament for the treatment of a cancer; methods of treating a cancer in a subject in need thereof comprising administering to said subject a jointly therapeutically effective amount of said combination; pharmaceutical compositions comprising such combination and commercial packages thereto.

Abstract: The present disclosure pertains to a pharmaceutical combination comprising (a) an alpha-isoform specific PI3K inhibitor, (b) an MDM2 inhibitor, and optionally (c) a BCL-2 inhibitor; combined preparations and pharmaceutical compositions thereof; the uses of such combination in the treatment or prevention of cancer; and methods of treating or preventing cancer a subject in need thereof comprising administering a therapeutically effective amount of such combination.

Abstract: The present disclosure pertains to a pharmaceutical combination comprising (a) alpha-isoform specific PI3K inhibitor and (b) an AKT inhibitor; combined preparations and pharmaceutical compositions thereof; the uses of such combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject in need thereof comprising administering a therapeutically effective amount of such combination.

Abstract: The present disclosure relates to pharmaceutical combinations comprising a cyclin dependent kinase 4/6 (CDK4/6) inhibitor compound, (b) a B-Raf inhibitor compound, and optionally (c) an alpha-isoform specific phosphatidylinositol 3-kinase (PI3K) inhibitor compound, for the treatment or prevention of cancer, as well as related pharmaceutical compositions, uses, and methods of treatment or prevention of cancer.

Abstract: The present disclosure relates to pharmaceutical combinations comprising (a) a cyclin dependent kinase 4/6 (CDK4/6) inhibitor compound, and (b) an epidermal growth factor receptor (EGFR) inhibitor, for the treatment or prevention of cancer. The disclosure also provides related pharmaceutical compositions, uses, and methods of treatment or prevention of cancer.

Abstract: The present disclosure relates to a pharmaceutical combination comprising (a) alpha-isoform specific PI3K inhibitor and (b) a B-RAF inhibitor; combined preparations and pharmaceutical compositions thereof; the uses of such combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject comprising administering a therapeutically effective amount of such combination.

Abstract: The present disclosure pertains to a pharmaceutical combination comprising (a) an alpha-isoform specific P13K inhibitor, (b) a cyclin dependent kinase 4/6 (CDK4/6) inhibitor, and (c) an antimetabolite antineoplastic agent; combined preparations and pharmaceutical compositions thereof; the uses of such a combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject comprising administering a therapeutically effective amount of such combination.

Abstract: Reversing resistance to a B-Raf inhibitor for the treatment of a proliferative disease by obtaining a tumor sample from the patient and testing it for genetic alterations in a panel of genes comprising BRAF, CRAF, CCND1, CDK4, HER2, IGF-1R, cMET, FGFR1, FGFR2, FGFR3 EGFR, MAP2K1, MAP2K2, NRAS, KRAS HRAS, PTEN, PIK3CA, and P16 and administering a drug combination therapy comprising the B-Raf inhibitor and a second inhibitor which overcomes resistance to the B-Raf inhibitor, which second inhibitor is selected based on genetic alterations discovered in the tumor sample.

Abstract: Compositions and methods are provided for diagnosis, prognosis and treatment of AR-related diseases, such as prostate diseases, such as prostate cancer, breast cancer, and many other diseases. In particular, a novel and clinically relevant mutation at position 877 of the androgen receptor (AR) has been identified. Drug sensitivity can be predicted and therapeutic regimens can be planned on the basis of the presence or absence of this mutation. Polypeptides comprising, antibodies to, and polynucleotides encoding the mutant AR can be used to identity novel treatments. A double mutation in AR at positions 742 and 878 is also shown to be useful for patient stratification.

Abstract: Reversing resistance to a B-Raf inhibitor for the treatment of a proliferative disease by obtaining a tumor sample from the patient and testing it for genetic alterations in a panel of genes comprising BRAF, CRAF, CCND1, CDK4, HER2, IGF-1R, cMET, FGFR1, FGFR2, FGFR3 EGFR, MAP2K1, MAP2K2, NRAS, KRAS HRAS, PTEN, PIK3CA, and P16 and administering a drug combination therapy comprising the B-Raf inhibitor and a second inhibitor which overcomes resistance to the B-Raf inhibitor, which second inhibitor is selected based on genetic alterations discovered in the tumor sample.

Abstract: The invention provides methods of monitoring differential gene expression of biomarkers to determine patient sensitivity to Cyclin Dependent kinase inhibitors (CDKi), methods of determining the sensitivity of a cell to a CDKi, methods of treating a patient with a CDKi and methods of screening for candidate CDKi.

Abstract: A combination of a CDK4/6 inhibitor and a MEK inhibitor for the treatment of diseases such as cancer.

Abstract: A pharmaceutical combination comprising (a) CDK4/6 inhibitor (b) a B-Raf inhibitor, and optionally (c) a MEK 1/2 inhibitor; combined preparations and pharmaceutical compositions thereof; 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: A pharmaceutical combination comprising (a) a B-Raf inhibitor, (b) a EGFR inhibitor and, optionally, (c) a PI3K inhibitor; 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.