Abstract: The present invention provides a pharmaceutical combination comprising a CRAF inhibitor in combination with (i) an ERK inhibitor or (ii) a MEK inhibitor or (iii) a CDK4/6 inhibitor, each as defined herein, or independently in each case a pharmaceutically acceptable salt thereof, for use in the treatment of NRAS-mutant melanoma and in the treatment of BRAF-mutant melanoma. wherein the melanoma may be unresectable and/or metastatic melanoma.

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 invention relates to a pharmaceutical combination comprising (a) a Raf inhibitor as defined herein (naporafenib), or a pharmaceutically acceptable salt thereof and (b) a MEK inhibitor, particularly trametinib, particularly for use in the treatment of sarcoma. This invention also relates to uses of such combination for preparation of a medicament for the treatment of a proliferative disease; methods of treating a proliferative disease in a patient in need thereof comprising administering to said patient a jointly therapeutically effective amount of said combination; use of such combination for the treatment of proliferative disease; pharmaceutical compositions comprising such combination and commercial packages thereto.

Abstract: The present invention provides a pharmaceutical combination comprising a CRAF inhibitor plus (i) an ERK inhibitor or (ii) a MEK inhibitor, for use in the treatment of non-small cell lung cancer (NSCLC) where the carcinoma cells of the NSCLC harbor a mutation of BRAF other than the BRAF V600E-mutant, and related invention aspects. The present invention also provides dosages and dosage regimens of a CRAF inhibitor with an ERK inhibitor or with trametinib for use in the treatment of BRAF V600 mutant (e.g. BRAF V600E mutant) NSCLC.

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 invention relates to a pharmaceutical combination comprising (a) an MDM2 inhibitor and (b) an ERK inhibitor, for use in the treatment of a cancer. This invention 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 kits and/or packages containing such combinations.

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 combination treatment which comprises (a) at least one ERK inhibitor preferably Compound B as described herein, and (b) a c-RAF inhibitor or a pharmaceutically acceptable salt thereof, preferably Compound A, which may be combined into a single pharmaceutical composition or prepared for separate or sequential administration. It includes a c-RAF inhibitor and an ERK inhibitor prepared for simultaneous, separate or sequential administration for the treatment of a proliferative disease, particularly an advanced solid tumor that harbors a Mitogen-activated protein kinase (MAPK) alteration, and includes methods of using these compounds in combination as well as 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 relates to pharmaceutical combinations comprising a cyclin dependent kinase 4/6 (CDdK4/6) inhibitor compound, (b) a B-Raf inhibitor compound, and optionally (c) an aipha-isoform specific phosphatidylinositol 3-kinase (P13K) 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 invention relates to a combination treatment which comprises (a) at least one ERK inhibitor preferably Compound B as described herein, and (b) a c-RAF inhibitor or a pharmaceutically acceptable salt thereof, preferably Compound A, which may be combined into a single pharmaceutical composition or prepared for separate or sequential administration. It includes a c-RAF inhibitor and an ERK inhibitor prepared for simultaneous, separate or sequential administration for the treatment of a proliferative disease, particularly an advanced solid tumor that harbors a Mitogen-activated protein kinase (MAPK) alteration, and includes methods of using these compounds in combination as well as a commercial package comprising such combination.

Abstract: The present invention relates to a pharmaceutical combination comprising (a) an MDM2 inhibitor and (b) an ERK inhibitor, for use in the treatment of a cancer. This invention 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 kits and/or packages containing such combinations.

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: 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: 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: 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 present disclosure relates to pharmaceutical combinations comprising a cyclin dependent kinase 4/6 (CDK4/6) inhibitor compound, (b) a mitogen activated protein kinase (MEK) 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 invention relates to a combination treatment which comprises (a) at least one ERK inhibitor preferably Compound B as described herein, and (b) a c-RAF inhibitor or a pharmaceutically acceptable salt thereof, preferably Compound A, which may be combined into a single pharmaceutical composition or prepared for separate or sequential administration. It includes a c-RAF inhibitor and an ERK inhibitor prepared for simultaneous, separate or sequential administration for the treatment of a proliferative disease, particularly an advanced solid tumor that harbors a Mitogen-activated protein kinase (MAPK) alteration, and includes methods of using these compounds in combination as well as a commercial package comprising such 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.