Combination therapies comprising anti-erbb3 agents

Abstract

Disclosed are methods and compositions for inhibiting the growth of a tumor (e.g., a malignant 5 tumor) in a subject. In particular, combination therapies for treating a tumor in a subject by coadministering an agent selected from i) an effective amount of an anti-estrogen agent; ii) an effective amount of a receptor tyrosine kinase inhibitor; iii) an effective amount of a MEK/PI3 kinase/AKT inhibitor; iv) an effective amount of MM-151; v) an effective amount of an mTOR inhibitor; and/or vi) an effective amount of trastuzumab or T-DM 1, and/or combinations thereof; and an effective amount of a 10 bispecific anti-ErbB2/anti-ErbB3 antibody.

1 . A method of treating a subject having a malignant tumor, the method comprising administering to the subject an effective amount a combination therapy comprising one or more agents selected from the group consisting of i) an anti-estrogen agent, ii) a receptor tyrosine kinase inhibitor, iii) a MEK inhibitor, iv) a PI3 kinase inhibitor, v) an AKT inhibitor, vi) an mTOR inhibitor, vii) trastuzumab, viii) ado-trastuzumab emtansine, ix) capecitabine, x) cisplatin, and xi) nab-paclitaxel; and an effective amount of an agent that is a bispecific anti-ErbB2/anti-ErbB3 antibody. 
     
     
         2 . The method of  claim 1 , wherein the anti-estrogen agent is an estrogen receptor antagonist or an aromatase inhibitor. 
     
     
         3 . The method of  claim 2 , wherein the estrogen receptor antagonist is fulvestrant or tamoxifen. 
     
     
         4 . The method of  claim 2 , wherein the aromatase inhibitor is letrozole, exemestane, anastrozole, aminoglutethimide, testolactone, vorozole, formestane, or fadrozole. 
     
     
         5 . The method of  claim 4 , wherein the aromatase inhibitor is letrozole. 
     
     
         6 . The method of  claim 1 , wherein the administration to the subject of the combination therapy does not create a drug-drug interaction-mediated toxicity in the subject. 
     
     
         7 . The method of  claim 1 , wherein the administration to the subject of the combination therapy creates a substantially additive or superadditive effect as compared to the separate administration of each of the combination therapy agents alone. 
     
     
         8 . The method of  claim 1 , wherein the receptor tyrosine kinase inhibitor is erlotinib, afatinib, dasatinib, gefitinib, imatinib, pazopinib, lapatinib, sunitinib, nilotinib, or sorafenib. 
     
     
         9 . The method of  claim 8 , wherein the receptor tyrosine kinase inhibitor is lapatinib. 
     
     
         10 . The method of  claim 1 , further comprising co-administration to the patient of an effective amount of either or both of capecitabine and cisplatin. 
     
     
         11 .- 17 . (canceled) 
     
     
         18 . An aqueous solution comprising a bispecific anti-ErbB2/anti-ErbB3 antibody and one or more of i) an anti-estrogen agent, ii) a receptor tyrosine kinase inhibitor, iii) a MEK inhibitor, iv) a PI3 kinase inhibitor, v) an AKT inhibitor, vi) an mTOR inhibitor, vii) trastuzumab, viii) ado-trastuzumab emtansine, ix) capecitabine, x) cisplatin, and xi) nab-paclitaxel. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein said MEK inhibitor is selumetinib, trametinib, UO126, or PD0325901, said PI3K inhibitor is BKM-120 or GDC-0941, and said AKT inhibitor is triciribine or MK-2206. 
     
     
         21 . (canceled) 
     
     
         22 . The aqueous solution of  claim 18 , wherein said MEK inhibitor is selumetinib, trametinib, UO126, or PD0325901, said PI3K inhibitor is BKM-120 or GDC-0941, and said AKT inhibitor is triciribine or MK-2206. 
     
     
         23 . The method of  claim 1 , comprising co-administering the MEK inhibitor and the bispecific anti-ErbB2/anti-ErbB3 antibody. 
     
     
         24 . The method of  claim 1 , comprising co-administering the PI3K inhibitor and the bispecific anti-ErbB2/anti-ErbB3 antibody. 
     
     
         25 . The method of  claim 1 , comprising co-administering the mTOR inhibitor and the bispecific anti-ErbB2/anti-ErbB3 antibody. 
     
     
         26 . The method of  claim 1 , comprising co-administering trastuzumab or ado-trastuzumab emtansine and the bispecific anti-ErbB2/anti-ErbB3 antibody. 
     
     
         27 . The method of  claim 1 , wherein said mTOR inhibitor is BEZ235, AZD8055, everolimus, temsirolimus, sirolimus, or ridaforolimus. 
     
     
         28 . The use of claim  11 , wherein said mTOR inhibitor is BEZ235, AZD8055, everolimus, temsirolimus, sirolimus, or ridaforolimus. 
     
     
         29 . The aqueous solution of  claim 18 , wherein said mTOR inhibitor is BEZ235, AZD8055, everolimus, temsirolimus, sirolimus, or ridaforolimus.