Pd-l1 antagonist combination treatments

Abstract

The present disclosure describes combination therapies comprising an antagonist of Programmed Death Ligand 1 receptor (PD-L1) and another therapeutic agent, and the use of the combination therapies for the treatment of cancer.

1 - 25 . (canceled) 
     
     
         26 . A method for treating a cancer in a subject comprising administering to the subject a combination therapy which comprises an antagonist of a Programmed Death Ligand 1 protein (PD-L1) and a second agent, wherein the second agent is an anti-4-1BB antibody, an anti-M-CSF antibody, or an anti-OX40 antibody. 
     
     
         27 . The method of  claim 26 , wherein the PD-L1 antagonist is an anti-PD-L1 monoclonal antibody comprising three CDRs from a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 8 and three CDRs from a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 9; wherein the anti-4-1BB antibody comprises three CDRs from a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 18 and three CDRs from a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 19; wherein the anti-M-CSF antibody comprises three CDRs from a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 30 and three CDRs from a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 31; and wherein the anti-OX40 comprises three CDRs from a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 38 and three CDRs from a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 39. 
     
     
         28 . The method of  claim 26  or  27 , wherein the second agent is an anti-4-1BB antibody. 
     
     
         29 . The method of  claim 28 , wherein the PD-Ll antagonist is administered as a 1-hour intravenous infusion every 2 weeks at a dose of 10 mg/kg. 
     
     
         30 . The method of  claim 29 , wherein the anti-4-1BB antibody is administered at 100 mg as a 1-hour IV infusion once every 4 weeks on Day 1 of each cycle. 
     
     
         31 . The method of  claim 30 , wherein when the anti-4-1BB antibody and the PD-L1 antagonist are both administered on the same day, the anti-4-1BB antibody is administered first, followed by the avelumab infusion no more than 30 minutes after the end of the anti-4-1BB antibody infusion. 
     
     
         32 . (canceled) 
     
     
         33 . The method of  claim 28 , wherein the combination therapy further comprises a third agent, wherein the third agent is an anti-M-CSF antibody or an anti-OX40 antibody. 
     
     
         34 . The method of  claim 33 , wherein the anti-M-CSF antibody comprises a heavy chain variable region and a light chain variable region comprising the amino acid sequences shown in SEQ ID NO: 30 and SEQ ID NO: 31, respectively. 
     
     
         35 . The method of  claim 33 , wherein the anti-OX40 antibody comprises a heavy chain variable region and a light chain variable region comprising the amino acid sequences shown in SEQ ID NO: 38 and SEQ ID NO: 39, respectively. 
     
     
         36 . The method of  claim 26 , wherein the subject is a human. 
     
     
         37 . The method of  claim 26 , wherein the cancer is a solid tumor. 
     
     
         38 . The method of  claim 26 , wherein the PD-L1 antagonist is avelumab. 
     
     
         39 . The method of  claim 38 , wherein the PD-L1 antagonist is administered as an initial dose of at least about 5 mg/kg, or about 10 mg/kg. 
     
     
         40 . The method of  claim 39 , wherein the PD-L1 antagonist is administered about once a week, or about once every two, three, four, or five weeks; and the second agent is administered about once a week, or about once every two, three, four, or five weeks. 
     
     
         41 . The method of  claim 40 , wherein the PD-L1 antagonist is administered about once every two weeks; and the second agent is administered about once every two weeks. 
     
     
         42 . The method of  claim 26 , further comprising administering a chemotherapy, radiotherapy, or chemoradiotherapy to the subject. 
     
     
         43 . The method of  claim 42 , wherein the chemoradiotherapy comprises cisplatin and intensely modulated radiation therapy (IMIRT). 
     
     
         44 . The method of  claim 26 , wherein the cancer is diffuse large B-cell lymphoma (DLBCL) or Squamous Cell Carcinoma of the Head and Neck (SCCHN). 
     
     
         45 - 120 . (canceled) 
     
     
         121 . The method of  claim 26 , wherein the cancer is selected from the group consisting of bladder cancer, breast cancer, colon cancer, clear cell kidney cancer, head/neck squamous cell carcinoma, lung squamous cell carcinoma, malignant melanoma, non-small-cell lung cancer (NSCLC), ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, small-cell lung cancer (SCLC), triple negative breast cancer, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, Hodgkin's lymphoma (HL), mantle cell lymphoma (MCL), multiple myeloma (MM), myeloid cell leukemia-1 protein (Mcl-1), myelodysplastic syndrome (MDS), non-Hodgkin's lymphoma (NHL), small lymphocytic lymphoma (SLL), Merkel cell carcinoma, Squamous Cell Carcinoma of the Head and Neck (SCCHN), and adrenocortical carcinoma (ACC). 
     
     
         122 - 123 . (canceled) 
     
     
         124 . The method of  claim 121 , wherein the cancer is advanced NSCLC, RCC, or urothelial cancer (UC), and wherein the cancer has progressed on one or more prior therapies.