Anti-egfr combinations for treating tumors

A combination, consisting of:

• (i) a pharmaceutical composition consisting of an admixture of 1) an effective amount of an EGFR binding antagonist antibody, and 2) one or more pharmaceutically acceptable carriers, excipients or diluents;
• (ii) a pharmaceutical composition consisting of an admixture of 1) an effective amount of an immunotherapeutic, and 2) one or more pharmaceutically acceptable carriers, excipients or diluents, wherein the immunotherapeutic is a compound of Formula (I):
• wherein dashed line represents bond or absence of bond;
• X is S or —NR1, R1 is —W0—W1—W2—W3—W4,
• W0 is a bond, alkyl, alkenyl, alkynyl, alkoxy, or -alkyl-S-alkyl-,
• W1 is a bond, —O—, or —NR2—, wherein R2 is hydrogen, alkyl or alkenyl,
• W2 is a bond, —O—, —C(O)—, —C(S)—, or —S(O)2—,
• W3 is a bond, —NR3—, wherein R3 is hydrogen, alkyl or alkenyl,
• W4 is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, aryloxy, heteroaryl, or heterocyclyl, each of which is optionally substituted by one or more substituents selected from the group consisting of hydroxyl, alkoxy, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, —NH2, nitro, -alkyl-hydroxyl, -alkyl-aryl, -alkyl-heteroaryl, -alkyl-heterocyclyl, —O—R4, —O-alkyl-R4, -alkyl-O—R4, —C(O)—R4, -alkyl-C(O)—R4, -alkyl-C(O)—O—R4, —C(O)—O—R4, —S—R4, —S(O)2—R4, —NH—S(O)2—R4, -alkyl-S—R4, -alkyl-S(O)2—R4, —NHR4, —NR4R4, —NH-alkyl-R4, halogen, —CN, —NO2, and —SH, wherein R4 is independently hydrogen, alkyl, alkenyl, -alkyl-hydroxyl, aryl, heteroaryl, heterocyclyl, or haloalkyl;
• Z is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, haloalkyl, heteroaryl, heterocyclyl, each of which can be optionally substituted by one or more substituents selected from the group consisting of hydroxyl, alkoxy, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, halogen, cyano, nitro, —N(R5)2, -alkoxy-alkyl, -alkoxy-alkenyl, —C(O)-alkyl, —C(O)—O-alkyl, —O—C(O)-alkyl, —C(O)—N(R5)2, aryl, heteroaryl, —CO-aryl, and —CO-heteroaryl, wherein each R5 is independently hydrogen, alkyl, haloalkyl, -alkyl-aryl, or -alkyl-heteroaryl;
• R is hydrogen, alkyl, alkoxy, haloalkyl, halogen, aryl, heteroaryl, heterocyclyl, each of which is optionally substituted by one or more substituents selected from the group consisting of hydroxyl, alkoxy, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, —NH2, nitro, -alkyl-hydroxyl, -alkyl-aryl, -alkyl-heteroaryl, -alkyl-heterocyclyl, —O—R4, —O-alkyl-R4, -alkyl-O—R4, —C(O)—R4, —C(O)—NH—R4, —C(O)—NR4R4, -alkyl-C(O)—R4, -alkyl-C(O)—O—R4, —C(O)—O—R4, —O—C(O)—R4, —S—R4, —C(O)—S—R4, —S—C(O)—R4, —S(O)2—R4, —NH—S(O)2—R4, -alkyl-S—R4, -alkyl-S(O)2—R4, —NHR4, —NR4R4, —NH-alkyl-R4 halogen, —CN, and —SH, wherein R4 is independently hydrogen, alkyl, alkenyl, alkoxy, -alkyl-hydroxyl, aryl, heteroaryl, heterocyclyl, or haloalkyl;
• n is 0, 1, 2, 3, or 4;
• Y is —NR6R7, —CR6R7R8, or -alkyl-NH2, each of which can be optionally substituted by one or more substituents selected from the group consisting of hydroxyl, alkoxy, alkyl, alkenyl, alkynyl, —NH2, halogen, —N(R5)2, -alkoxy-alkyl, -alkoxy-alkenyl, —C(O)-alkyl, —C(O)—O-alkyl, —C(O)—N(R5)2, aryl, heteroaryl, —CO-aryl, and —CO-heteroaryl,
• wherein R6, R7 and R8 are independently hydrogen, alkyl, alkenyl, alkoxy, alkylamino, dialkylamino, alkylthio, arylthio, -alkyl-hydroxyl, -alkyl-C(O)—O—R9, -alkyl-C(O)—R9, or -alkyl-O—C(O)—R9, wherein each R5 is independently hydrogen, alkyl, haloalkyl, -alkyl-aryl, or -alkyl-heteroaryl, wherein R9 is hydrogen, alkyl, alkenyl, halogen, or haloalkyl;
• X and Z taken together may optionally form a (5-9)-membered ring,
• or a pharmaceutically acceptable salt or solvate thereof, that is capable of activating a human plasmacytoid dendritic cell, myeloid dendritic cell, or NK cell, or a combination thereof;
• and, optionally,
• (iii) an effective amount of an additional therapeutic agent, wherein the additional therapeutic agent is an anticancer agent selected from the group consisting of a chemotherapeutic agent, an antimetabolite, an inhibitor of topoisomerase I and II, an alkylating agent, a microtubule inhibitor, an antiandrogen agent, a GNRh modulator or mixtures thereof;
• wherein the EGFR binding antagonist antibody and the immunotherapeutic are not covalently linked.