Anti-CSF1R Antibody and Anti-PD-1 Antibody Combination Therapy for Cancer

Abstract

Methods of treating cancer with antibodies that bind colony stimulating factor 1 receptor (CSF1R) in combination with PD-1/PD-L1 inhibitors are provided.

1 .- 64 . (canceled) 
     
     
         65 . A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an anti-CSF1R antibody and an anti-PD-1 antibody, 
       wherein the anti-PD-1 antibody is selected from:
 i) an antibody comprising a heavy chain comprising the sequence of SEQ ID NO: 100 and a light chain comprising the sequence of SEQ ID NO: 102; 
 ii) an antibody comprising a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 105, an HC CDR2 having the sequence of SEQ ID NO: 107, and an HC CDR3 having the sequence of SEQ ID NO: 109, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 112, a LC CDR2 having the sequence of SEQ ID NO: 114, and a LC CDR3 having the sequence of SEQ ID NO: 116; and 
 iii) an antibody comprising a heavy chain comprising the sequences of SEQ ID NOs: 100 and 101 and a light chain comprising the sequences of SEQ ID NOs: 102 and 103. 
 
     
     
         66 . A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an anti-CSF1R antibody and an anti-PD-1 antibody, wherein the anti-PD-1 antibody is nivolumab. 
     
     
         67 . The method of  claim 65 , wherein the anti-CSF1R antibody and the anti-PD-1 antibody are administered concurrently or sequentially. 
     
     
         68 . The method of  claim 67 , wherein the anti-CSF1R antibody and the anti-PD-1 antibody are administered concurrently. 
     
     
         69 . The method of  claim 67 , wherein one or more doses of the anti-PD-1 antibody are administered prior to administering the anti-CSF1R antibody. 
     
     
         70 . The method of  claim 69 , wherein the subject received a complete course of anti-PD-1 antibody therapy prior to administration of the anti-CSF1R antibody. 
     
     
         71 . The method of  claim 70 , wherein the anti-CSF1R antibody is administered during a second course of anti-PD-1 antibody therapy. 
     
     
         72 . The method of  claim 69 , wherein the subject received at least one, at least two, at least three, or at least four doses of the anti-PD-1 antibody prior to administration of the anti-CSF1R antibody. 
     
     
         73 . The method of  claim 65 , wherein at least one dose of the anti-PD-1 antibody is administered concurrently with the anti-CSF1R inhibitor. 
     
     
         74 . The method of  claim 67 , wherein one or more doses of the anti-CSF1R antibody are administered prior to administering the anti-PD-1 antibody. 
     
     
         75 . The method of  claim 74 , wherein the subject received at least two, at least three, or at least four doses of the anti-CSF1R antibody prior to administration of the anti-PD-1 antibody. 
     
     
         76 . The method of  claim 74 , wherein at least one dose of the anti-CSF1R antibody is administered concurrently with the anti-PD-1 antibody. 
     
     
         77 . The method of  claim 65 , wherein the anti-PD-1 antibody is administered at a dose of about 0.5-10 mg/kg, such as at a dose of about 0.5, about 1, about 2, about 3, about 4, about 5, or about 10 mg/Kg. 
     
     
         78 . The method of  claim 77 , wherein the anti-PD-1 antibody is administered at a dose of 3 mg/kg. 
     
     
         79 . The method of  claim 65 , wherein the anti-CSF1R antibody and the anti-PD-1 antibody are administered once per 1, 2, 3, 4, or 5 weeks, such as once per week, or such as once every 2 weeks, or once every 3 weeks. 
     
     
         80 . The method of  claim 79 , wherein the anti-PD-1 antibody is administered every 4 weeks. 
     
     
         81 . The method of  claim 65 , wherein the anti-PD-1 antibody is nivolumab and is administered at a dose of 240 mg every 2 weeks. 
     
     
         82 . The method of  claim 65 , wherein the cancer is recurrent or progressive after a therapy selected from surgery, chemotherapy, radiation therapy, or a combination thereof. 
     
     
         83 . The method of  claim 65 , wherein administration of the anti-CSF1R antibody and the anti-PD-1 antibody results in synergistic inhibition of tumor growth in a mouse model of the cancer. 
     
     
         84 . The method of  claim 65 , wherein the cancer is a colon, rectum, or colorectal cancer and the mouse model comprises colorectal carcinoma cells, such as MC38 colorectal carcinoma cells. 
     
     
         85 . The method of  claim 65 , wherein the cancer is a pancreatic cancer and the mouse model comprises murine pancreatic ductal adenocarcinoma (PDAC) cells, such as KRasG12D/Ink4a−/− pancreatic ductal adenocarcinoma cells. 
     
     
         86 . A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an anti-CSF1R antibody and an anti-PD-1 antibody;
 (a) wherein the anti-PD-1 antibody is administered at a dose of 240 mg every two weeks; and   (b) wherein the anti-PD-1 antibody is selected from:
 i) an antibody comprising a heavy chain comprising the sequence of SEQ ID NO: 100 and a light chain comprising the sequence of SEQ ID NO: 102; 
 ii) an antibody comprising a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 105, an HC CDR2 having the sequence of SEQ ID NO: 107, and an HC CDR3 having the sequence of SEQ ID NO: 109, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 112, a LC CDR2 having the sequence of SEQ ID NO: 114, and a LC CDR3 having the sequence of SEQ ID NO: 116; and 
 iii) an antibody comprising a heavy chain comprising the sequences of SEQ ID NOs: 100 and 101 and a light chain comprising the sequences of SEQ ID NOs: 102 and 103. 
   
     
     
         87 . A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an anti-CSF1R antibody and an anti-PD-1 antibody;
 (a) wherein the anti-PD-1 antibody is administered at a dose of 240 mg every two weeks; and   (b) wherein the anti-PD-1 antibody is nivolumab.   
     
     
         88 . A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an anti-CSF1R antibody and an anti-PD-1 antibody;
 (a) wherein the anti-PD-1 antibody is administered at a flat dose every four weeks; and   (b) wherein the anti-PD-1 antibody is selected from:
 i) an antibody comprising a heavy chain comprising the sequence of SEQ ID NO: 100 and a light chain comprising the sequence of SEQ ID NO: 102; 
 ii) an antibody comprising a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 105, an HC CDR2 having the sequence of SEQ ID NO: 107, and an HC CDR3 having the sequence of SEQ ID NO: 109, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 112, a LC CDR2 having the sequence of SEQ ID NO: 114, and a LC CDR3 having the sequence of SEQ ID NO: 116; and 
 iii) an antibody comprising a heavy chain comprising the sequences of SEQ ID NOs: 100 and 101 and a light chain comprising the sequences of SEQ ID NOs: 102 and 103. 
   
     
     
         89 . A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an anti-CSF1R antibody and an anti-PD-1 antibody;
 (a) wherein the anti-PD-1 antibody is administered at a flat dose every four weeks; and   (b) wherein the anti-PD-1 antibody is nivolumab.