Combination of a PD-1 antagonist and a RAF inhibitor for treating cancer

A method for the delay of progression or treatment of cancer in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a PD-1 antagonist in combination with a therapeutically effective amount of a RAF inhibitor,

• wherein the cancer is associated with a B-Raf mutation or a K-Ras mutation, wherein the cancer is a lung cancer or a colon cancer;
• wherein the PD-1 antagonist is an antibody or an antigen binding fragment thereof, which specifically binds to human PD-1 and which comprises a heavy chain variable region (Vh) and a light chain variable region (Vk), wherein the Vh comprises complementarity determining region (CDR)1, CDR2, and CDR3 comprising SEQ ID NOs:
• 31, 32, and 33, respectively;
• and the Vk comprises CDR1, CDR2, CDR3 comprising SEQ ID NO:
• 34, 35, and 36, respectively;
• and
• wherein the RAF inhibitor is a compound of Formula (I),
• or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:
• X is selected from CH2 and O;
• R8, R9, R10 and R11, which may be the same or different, are each selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkynyl, —NR13R14, —OR13 , —COR13, —CO2R13, —CONR13R14, —C(═NR13)NR14R15, —NR13COR14, —NR13CONR14R15, —NR13C O2R14, —SO2R13, —SO2aryl, —NR13S O2NR14R15, and —NR13SO2R14, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, aryl, and heterocyclyl are each optionally substituted with at least one substituent R16, or (R8 and R9), and/or (R9 and R10), and/or (R10 and R11) together with the ring to which they are attached, form a fused ring selected from the group consisting of heterocyclyl and heteroaryl rings optionally substituted with at least one substituent R16;
• R13, R14 and R15, which may be the same or different, are each selected from the group consisting of H, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• or (R13 and R14), and/or (R14 and R15) together with the atom(s) to which they are attached, each form a ring selected from the group consisting of heterocyclyl and heteroaryl rings optionally substituted with at least one substituent R16;
• R16 is selected from the group consisting of halogen, haloalkyl, alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, alkynyl, oxo, —CN, —OR′, —NR′R″, —COR′, —CO2R′, —CONR′R″, —C(═NR′)NR″R′″, —NR′COR″, —NR′CONR′R″, —NR′CO2R″, —SO2R′, —SO2aryl, —NR′S O2NR″R′″, —NR′O2R″, and —NR′SO2aryl, wherein R′, R″, and R′″ are independently selected from the group consisting of H, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, or (R′ and R″), and/or (R″ and R′″) together with the atoms to which they are attached, form a ring selected from the group consisting of heterocyclyl and heteroaryl rings.