Combination Therapy for the Treatment of Cancer

Abstract

This invention relates to a pharmaceutical composition that comprises a first molecule that specifically binds HER2/neu and a second molecule that specifically binds a cell-surface receptor (or its ligand) that is involved in regulating an immune checkpoint (or the ligand thereof). The invention particularly relates to the embodiment wherein the second molecule binds to PD-1. The invention also relates to the use of such pharmaceutical compositions to treat cancer and other diseases.

1 - 28 . (canceled) 
     
     
         29 . A method of treating cancer, comprising administering to a subject in need thereof a Variant Chimeric 4D5 Antibody comprising a light chain variable domain comprising the amino acid sequence of SEQ ID NO:4, and a heavy chain comprising an amino acid sequence of SEQ ID NO:11, and an anti-PD-1 antibody, wherein said anti-PD-1 antibody is:
 (a) PD-1 mAb 6-ISQ, that comprises a light chain that comprises the amino acid sequence of SEQ ID NO:87 and a heavy chain that comprises the amino acid sequence of SEQ ID NO:88; or   (b) pembrolizumab, and   wherein said cancer is a cancer in which HER2/neu is expressed.   
     
     
         30 . The method of  claim 29 , wherein:
 (a) said Variant Chimeric 4D5 Antibody is administered at a dosage of approximately 15 mg/kg and said anti-PD-1 antibody is administered at a fixed dosage of approximately 100-500 mg; or   (b) said Variant Chimeric 4D5 Antibody is administered or formulated to be administered at a dosage of approximately 6-18 mg/kg and said anti-PD-1 antibody is administered at a dosage of approximately 1-10 mg/kg.   
     
     
         31 . The method of  claim 29 , wherein said Variant Chimeric 4D5 Antibody and said anti-PD-1 antibody are administered every three weeks. 
     
     
         32 . The method of  claim 30 , wherein said Variant Chimeric 4D5 Antibody and said anti-PD-1 antibody are administered every three weeks. 
     
     
         33 . The method of  claim 29 , wherein said Variant Chimeric 4D5 Antibody and said anti-PD-1 antibody are administered concurrently to said subject in separate pharmaceutical compositions, wherein said separate compositions are administered within a 24-hour period. 
     
     
         34 . The method of  claim 30 , wherein said Variant Chimeric 4D5 Antibody and said anti-PD-1 antibody are administered concurrently to said subject in separate pharmaceutical compositions, wherein said separate compositions are administered within a 24-hour period. 
     
     
         35 . The method of  claim 31 , wherein said Variant Chimeric 4D5 Antibody and said anti-PD-1 antibody are administered concurrently to said subject in separate pharmaceutical compositions, wherein said separate compositions are administered within a 24-hour period. 
     
     
         36 . The method of  claim 32 , wherein said Variant Chimeric 4D5 Antibody and said anti-PD-1 antibody are administered concurrently to said subject in separate pharmaceutical compositions, wherein said separate compositions are administered within a 24-hour period. 
     
     
         37 . The method of  claim 29 , wherein said cancer is a breast cancer, gastric cancer, prostate cancer, uterine cancer, ovarian cancer, colon cancer, endometrial cancer, adrenal carcinoma, non-small cell lung cancer, head and neck cancer, laryngeal cancer, liver cancer, renal cancer, glioblastoma, or pancreatic cancer. 
     
     
         38 . The method of  claim 30 , wherein said cancer is a breast cancer, gastric cancer, prostate cancer, uterine cancer, ovarian cancer, colon cancer, endometrial cancer, adrenal carcinoma, non-small cell lung cancer, head and neck cancer, laryngeal cancer, liver cancer, renal cancer, glioblastoma, or pancreatic cancer. 
     
     
         39 . The method of  claim 31 , wherein said cancer is a breast cancer, gastric cancer, prostate cancer, uterine cancer, ovarian cancer, colon cancer, endometrial cancer, adrenal carcinoma, non-small cell lung cancer, head and neck cancer, laryngeal cancer, liver cancer, renal cancer, glioblastoma, or pancreatic cancer. 
     
     
         40 . The method of  claim 32 , wherein said cancer is a breast cancer, gastric cancer, prostate cancer, uterine cancer, ovarian cancer, colon cancer, endometrial cancer, adrenal carcinoma, non-small cell lung cancer, head and neck cancer, laryngeal cancer, liver cancer, renal cancer, glioblastoma, or pancreatic cancer. 
     
     
         41 . The method of  claim 33 , wherein said cancer is a breast cancer, gastric cancer, prostate cancer, uterine cancer, ovarian cancer, colon cancer, endometrial cancer, adrenal carcinoma, non-small cell lung cancer, head and neck cancer, laryngeal cancer, liver cancer, renal cancer, glioblastoma, or pancreatic cancer. 
     
     
         42 . The method of  claim 34 , wherein said cancer is a breast cancer, gastric cancer, prostate cancer, uterine cancer, ovarian cancer, colon cancer, endometrial cancer, adrenal carcinoma, non-small cell lung cancer, head and neck cancer, laryngeal cancer, liver cancer, renal cancer, glioblastoma, or pancreatic cancer. 
     
     
         43 . The method of  claim 35 , wherein said cancer is a breast cancer, gastric cancer, prostate cancer, uterine cancer, ovarian cancer, colon cancer, endometrial cancer, adrenal carcinoma, non-small cell lung cancer, head and neck cancer, laryngeal cancer, liver cancer, renal cancer, glioblastoma, or pancreatic cancer. 
     
     
         44 . The method of  claim 36 , wherein said cancer is a breast cancer, gastric cancer, prostate cancer, uterine cancer, ovarian cancer, colon cancer, endometrial cancer, adrenal carcinoma, non-small cell lung cancer, head and neck cancer, laryngeal cancer, liver cancer, renal cancer, glioblastoma, or pancreatic cancer. 
     
     
         45 . The method of  claim 29 , wherein said treatment further comprises the step of administering a third therapeutic agent, wherein said third therapeutic agent is selected from the group consisting of an anti-angiogenic agent, an anti-neoplastic agent, a chemotherapeutic agent, and a cytotoxic agent. 
     
     
         46 . The method of  claim 30 , wherein said treatment further comprises the step of administering a third therapeutic agent, wherein said third therapeutic agent is selected from the group consisting of an anti-angiogenic agent, an anti-neoplastic agent, a chemotherapeutic agent, and a cytotoxic agent. 
     
     
         47 . The method of  claim 31 , wherein said treatment further comprises the step of administering a third therapeutic agent, wherein said third therapeutic agent is selected from the group consisting of an anti-angiogenic agent, an anti-neoplastic agent, a chemotherapeutic agent, and a cytotoxic agent. 
     
     
         48 . The method of  claim 32 , wherein said treatment further comprises the step of administering a third therapeutic agent, wherein said third therapeutic agent is selected from the group consisting of an anti-angiogenic agent, an anti-neoplastic agent, a chemotherapeutic agent, and a cytotoxic agent. 
     
     
         49 . The method of  claim 33 , wherein said treatment further comprises the step of administering a third therapeutic agent, wherein said third therapeutic agent is selected from the group consisting of an anti-angiogenic agent, an anti-neoplastic agent, a chemotherapeutic agent, and a cytotoxic agent. 
     
     
         50 . The method of  claim 34 , wherein said treatment further comprises the step of administering a third therapeutic agent, wherein said third therapeutic agent is selected from the group consisting of an anti-angiogenic agent, an anti-neoplastic agent, a chemotherapeutic agent, and a cytotoxic agent. 
     
     
         51 . The method of  claim 35 , wherein said treatment further comprises the step of administering a third therapeutic agent, wherein said third therapeutic agent is selected from the group consisting of an anti-angiogenic agent, an anti-neoplastic agent, a chemotherapeutic agent, and a cytotoxic agent. 
     
     
         52 . The method of  claim 36 , wherein said treatment further comprises the step of administering a third therapeutic agent, wherein said third therapeutic agent is selected from the group consisting of an anti-angiogenic agent, an anti-neoplastic agent, a chemotherapeutic agent, and a cytotoxic agent.