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 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 disclosure relates to use of a protein kinase C (PKC) inhibitor in the treatment or prevention of proliferative diseases. The disclosure also relates to corresponding pharmaceutical formulations, uses, methods, combinations, and related disclosure embodiments. The disclosure further relates to use of a pharmaceutical combination comprising a PKC inhibitor and another therapeutic agent, such as an MDM2 inhibitor, in the treatment or prevention of a proliferative disease.

Abstract: The present disclosure relates to use of a protein kinase C (PKC) inhibitor in the treatment or prevention of proliferative diseases. The disclosure also relates to corresponding pharmaceutical formulations, uses, methods, combinations, and related disclosure embodiments. The disclosure further relates to use of a pharmaceutical combination comprising a PKC inhibitor and another therapeutic agent, such as an MDM2 inhibitor, in the treatment or prevention of a proliferative disease.

Abstract: The present invention relates to a pharmaceutical combination comprising (a) a Raf inhibitor as defined herein, or a pharmaceutically acceptable salt thereof and (b) a MEK inhibitor, particularly trametinib, particularly for use in the treatment of a proliferative disease. 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 subject in need thereof comprising administering to said subject 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 relates to a pharmaceutical combination comprising (a) a Raf inhibitor as defined herein, or a pharmaceutically acceptable salt thereof and (b) a MEK inhibitor, particularly trametinib, particularly for use in the treatment of a proliferative disease. 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 subject in need thereof comprising administering to said subject 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 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 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 use of a protein kinase C (PKC) inhibitor in the treatment or prevention of proliferative diseases. The disclosure also relates to corresponding pharmaceutical formulations, uses, methods, combinations, and related disclosure embodiments. The disclosure further relates to use of a pharmaceutical combination comprising a PKC inhibitor and another therapeutic agent, such as an MDM2 inhibitor, in the treatment or prevention of a proliferative disease.

Abstract: The present invention relates to a pharmaceutical combination comprising (a) a Raf inhibitor as defined herein, or a pharmaceutically acceptable salt thereof and (b) a MEK inhibitor, particularly trametinib, particularly for use in the treatment of a proliferative disease. 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 subject in need thereof comprising administering to said subject 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 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: 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: 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 876 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 741 and 877 is also shown to be useful for patient stratification.