Combination therapies

A kit comprising:

• a) a pharmaceutical composition comprising a pan ErbB family inhibitor and b) a pharmaceutical composition comprising a KRas G12C inhibitor of:
• or a pharmaceutically acceptable salt thereof:
• wherein:
• X is a 4-12 membered saturated or partially saturated monocyclic, bridged or spirocyclic ring, wherein the saturated or partially saturated monocyclic ring is optionally substituted with one or more R8;
• Y is a bond, O, S or NR5;
• R1 is —C(O)C(RA)C(RB)p or —SO2C(RA)C(RB)p;
• R2 is hydrogen, alkyl, hydroxyalkyl, dihydroxyalkyl, alkylaminylalkyl, dialkylaminylalkyl, —Z—NR5R10, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, or heteroarylalkyl, wherein each of the Z, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, and heteroarylalkyl may be optionally substituted with one or more R9;
• each Z is C1-C4 alkylene;
• each R3 is independently C1-C3 alkyl, oxo, haloalkyl, hydroxyl or halogen;
• L is a bond, —C(O)—, or C1-C3 alkylene;
• R4 is hydrogen, cycloalkyl, heterocyclyl, aryl, aralkyl or heteroaryl, wherein each of the cycloalkyl, heterocyclyl, aryl, aralkyl and heteroaryl may be optionally substituted with one or more R6, R7 or R8;
• each R5 is independently hydrogen or C1-C3 alkyl;
• R6 is cycloalkyl, heterocyclyl, heterocyclylalkyl, aryl, or heteroaryl, wherein each of the cycloalkyl, heterocyclyl, aryl, or heteroaryl may be optionally substituted with one or more R7;
• each R7 is independently halogen, hydroxyl, C1-C6 alkyl, cycloalkyl, alkoxy, haloalkyl, amino, cyano, heteroalkyl, hydroxyalkyl or Q-haloalkyl, wherein Q is O or S;
• R8 is oxo, C1-C3 alkyl, C2-C4 alkynyl, heteroalkyl, cyano, —C(O)OR5, —C(O)N(R5)2, —N(R5)2, wherein the C1-C3 alkyl may be optionally substituted with cyano, halogen, —OR5, —N(R5)2, or heteroaryl;
• each R9 is independently hydrogen, oxo, acyl, hydroxyl, hydroxyalkyl, cyano, halogen, C1-C6 alkyl, aralkyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclylalkyl, alkoxy, dialkylaminyl, dialkylamidoalkyl, or dialkylaminylalkyl, wherein the C1-C6 alkyl may be optionally substituted with cycloalkyl;
• each R10 is independently hydrogen, acyl, C1-C3 alkyl, heteroalkyl or hydroxyalkyl;
• R11 is haloalkyl;
• RA is absent, hydrogen, deuterium, cyano, halogen, C1-C-3 alkyl, haloalkyl, heteroalkyl, —C(O)N(R5)2, or hydroxyalkyl;
• each RB is independently hydrogen, deuterium, cyano, C1-C3 alkyl, hydroxyalkyl, heteroalkyl, C1-C3 alkoxy, halogen, haloalkyl, —ZNR5R11, —C(O)N(R5)2, —NHC(O)C1-C3 alkyl, —CH2NHC(O)C1-C3 alkyl, heteroaryl, heteroarylalkyl, dialkylaminylalkyl, or heterocyclylalkyl wherein the heterocyclyl portion is substituted with one or more substituents independently selected from halogen, hydroxyl, alkoxy and C1-C3 alkyl, wherein the heteroaryl or the heteroaryl portion of the heteroarylalkyl is optionally substituted with one or more R7;
• when is a triple bond then RA is absent, RB is present and p equals one, or when is a double bond then RA is present, RB is present and p equals two, or RA, RB and the carbon atoms to which they are attached form a 5-8 membered partially saturated cycloalkyl optionally substituted with one or more R7;
• m is zero or an integer between 1 and 2;
• and
• p is one or two.
• or
• and pharmaceutically acceptable salts thereof, wherein R1, R3, R4, R5, R10, L and m are as defined for Formula I, R11 is hydrogen, methyl or hydroxyalkyl, and the piperidinyl ring is optionally substituted with R8 wherein R8 is as defined for Formula I
• or
• and pharmaceutically acceptable salts thereof, wherein R1, R3, R4, L and m are as defined for Formula I, R2 is heterocyclylalkyl optionally substituted with one or more R9 where R9 is as defined for Formula I, and the piperazinyl ring is optionally substituted with Re, where Re is as defined for Formula I,
• for treating cancer in a subject.