Anti-pd-l1 combinations for treating tumors

Abstract

The present invention relates to therapeutic combinations and methods for treating cancers using combination therapy.

1 . A combination, comprising:
 (i) an effective amount of a PD-L/PD-1 Axis antagonist antibody; and   (ii) an effective amount of an immunotherapeutic, wherein the immunotherapeutic is 4-amino-2-(ethoxymethyl)-a,a-di-methyl-1H-imidazo[4,5-c]quinoline-1-ethanol;   wherein the PD-L/PD-1 Axis antagonist antibody and the immunotherapeutic are not covalently linked to each other.   
     
     
         2 . The combination of  claim 1 , wherein said PD-L/PD-1 Axis antagonist is selected from the group consisting of a PD-1 binding antagonist, a PD-L1 binding antagonist and a PD-L2 binding antagonist. 
     
     
         3 . The combination of  claim 2 , wherein the PD-L/PD-1 Axis antagonist is a PD-1 binding antagonist. 
     
     
         4 . The combination of  claim 3 , wherein the PD-1 binding antagonist is an antibody fragment. 
     
     
         5 . The combination of  claim 5 , wherein the PD-1 binding antagonist is MDX-1106, Merck 3475, CT-011, AMP-224, or AMP-514. 
     
     
         6 . The combination of  claim 2 , wherein the PD-L/PD-1 Axis antagonist is a PD-L1 binding antagonist. 
     
     
         7 . The combination of  claim 6 , wherein the PD-L1 binding antagonist is an antibody. 
     
     
         8 . The combination of  claim 7 , wherein the PD-L1 binding antagonist is selected from the group consisting of: YW243.55.S70, MPDL3280A, MDX-1105, MEDI-4736, and MSB0010718C. 
     
     
         9 . The combination of  claim 2 , wherein the PD-L/PD-1 Axis antagonist is a PD-L2 binding antagonist. 
     
     
         10 . The combination of  claim 9 , wherein the PD-L2 binding antagonist is an antibody. 
     
     
         11 . The combination of  claim 9 , wherein the PD-L2 binding antagonist is an immunoadhesin. 
     
     
         12 . The combination of any one of  claim 1 , wherein said immunotherapeutics is a compound of any one of formula (I) to (XIXb), or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         13 . The combination of  claim 1 , further comprising an effective amount of an an anticancer agent. 
     
     
         14 . The combination of  claim 13 , wherein said anticancer agent is an antimetabolite, an inhibitor of topoisomerase I and II, an alkylating agent, a microtubule inhibitor, an antiandrogen agent, a GNRh modulator or mixtures thereof. 
     
     
         15 . The combination of  claim 13 , wherein said anticancer agent is a chemotherapeutic agent selected from the group consisting of tamoxifen, raloxifene, anastrozole, exemestane, letrozole, imatanib, paclitaxel, cyclophosphamide, lovastatin, minosine, gemcitabine, cytarabine, 5-fluorouracil, methotrexate, docetaxel, goserelin, vincristine, vinblastine, nocodazole, teniposide etoposide, gemcitabine, epothilone, vinorelbine, camptothecin, daunorubicin, actinomycin D, mitoxantrone, acridine, doxorubicin, epirubicin, or idarubicin. 
     
     
         16 . The combination of  claim 1 , wherein said immunotherapeutic is of an amount that is capable of:
 (1) inducing IFN-α in an enriched human blood DCs;   (2) inducing TNF-α in an enriched human blood DCs;   (3) inducing IL-12-α in an enriched human blood DCs;   (4) activating CD45+ immune cells in tumor microenvironment;   (5) activating CD4+ and CD8+ T cells in tumor microenvironment;   (6) activating NK cells in tumor microenvironment;   (7) activating plasmacytoid dendritic cells (pDC) and myeloid dendritic cells (mDc) in tumor microenvironment;   (8) activating macrophages and Monocytes in tumor microenvironment; and/or   (9) increasing migratory DCs in draining lymph nodes.   
     
     
         17 . A kit, comprising the combination of  claim 1 .