Abstract: The present invention relates to methods for treating cancer comprising administering an antagonist of PD-1, e.g., anti-PD-1 antibody or antigen binding fragment thereof, and an anti-CTLA4 antibody or antigen binding fragment thereof, wherein the CTLA4 antibody or antigen binding fragment thereof is given at a fixed dose. Also provided are compositions and kits comprising a dosage of an anti-PD-1 antibody and a dosage of an anti-CTLA4 antibody, and uses thereof.

Abstract: Provided herein are methods of treating cancer (e.g., melanoma or RCC), which comprise administering to a human patient in need thereof: (a) a PD-1 antagonist; (b) a CTLA4 antagonist; and (c) lenvatinib represented by Formula (I), or a pharmaceutically acceptable salt thereof. Also provided are kits containing such agents and uses of therapeutic combinations of such agents for the treatment of cancer.

Abstract: The present invention relates to method for treating cancer comprising administering an antagonist of PD-1, e.g., anti-PD-1 antibody or antigen binding fragment thereof, and an anti-CTLA4 antibody or antigen binding fragment thereof, wherein the CTLA4 antibody or antigen binding fragment thereof is given at a fixed dose. Also provided are compositions and kits comprising a dosage of an anti-PD-1 antibody and a dosage of an anti-CTLA4 antibody, and uses thereof.

Abstract: A novel combination comprising a B-Raf inhibitor, particularly N-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide or a pharmaceutically acceptable salt thereof, the MEK inhibitor N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)6,8-dimethyl;-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, and a PD-1 antagonist; pharmaceutical compositions comprising the same and methods of using such combinations and compositions in the treatment of conditions in which the inhibition of MEK and/or B-Raf and/or immune modulation through PD-1 is beneficial, eg. cancer.

Abstract: A novel combination comprising a B-Raf inhibitor, particularly N-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide or a pharmaceutically acceptable salt thereof, the MEK inhibitor N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)6,8-dimethyl; -2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, and a PD-1 antagonist; pharmaceutical compositions comprising the same and methods of using such combinations and compositions in the treatment of conditions in which the inhibition of MEK and/or B-Raf and/or immune modulation through PD-1 is beneficial, e.g., cancer.

Abstract: A novel combination comprising a B-Raf inhibitor, particularly N-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide or a pharmaceutically acceptable salt thereof, the MEK inhibitor N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)6,8-dimethyl; -2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, and a PD-1 antagonist; pharmaceutical compositions comprising the same and methods of using such combinations and compositions in the treatment of conditions in which the inhibition of MEK and/or B-Raf and/or immune modulation through PD-1 is beneficial, e.g., cancer.

Abstract: Among the different intrastrand quadruplex structures that can arise from duplex DNA, it has been discovered that the nucleotide sequences (GGA)4 (SEQ ID NO: 1) and (GGA)3GG (SEQ ID NO: 2) form biologically significant quadruplex structures. Thus, provided herein are methods for identifying molecules that modulate the biological activity of quadruplex DNA comprising the nucleotide sequence (GGA)4 (SEQ ID NO: 1) or the nucleotide sequence (GGA)3GG (SEQ ID NO: 2), and specifically, methods for identifying molecules that bind such quadruplexes. Also provided herein are methods for modulating the biological activity of a biologically significant native quadruplex DNA with a molecule identified by the methods described herein.

Abstract: Among the different intrastrand quadruplex structures that can arise from duplex DNA, it has been discovered that the nucleotide sequences (GGA)4 and (GGA)3GG form biologically significant quadruplex structures. Thus, provided herein are methods for identifying molecules that modulate the biological activity of quadruplex DNA comprising the nucleotide sequence (GGA)4 or the nucleotide sequence (GGA)3GG, and specifically, methods for identifying molecules that bind such quadruplexes. Also provided herein are methods for modulating the biological activity of a biologically significant native quadruplex DNA with a molecule identified by the methods described herein.