Combination therapy with anti-il-8 antibodies and anti-pd-1 antibodies for treating cancer

Abstract

Provided herein are methods for the clinical treatment of tumors (e.g., advanced solid tumors) in patients having certain levels of serum IL-8 using an anti-IL-8 antibody in combination with an anti-PD-1 antibody.

1 - 52 . (canceled) 
     
     
         53 . A method of treating a solid tumor in a human subject, the method comprising administering to the subject an effective amount of each of:
 (a) an anti-IL-8 antibody comprising CDR1, CDR2, and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO: 7, and CDR1, CDR2, and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO: 8,   (b) an anti-PD-1 antibody comprising CDR1, CDR2, and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO: 17, and CDR1, CDR2, and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO: 18, wherein the anti-IL-8 antibody is administered at a fixed dose of about 2400 mg to about 5000 mg once every two weeks or once every three weeks.   
     
     
         54 . The method of  claim 53 , wherein:
 (a) the anti-IL-8 antibody comprises heavy chain and light chain variable region CDRs comprising the amino acid sequences set forth in SEQ ID NOs: 1-3 and 4-6, respectively; and   (b) the anti-PD-1 antibody comprises heavy chain and light chain variable region CDRs comprising the amino acid sequences set forth in SEQ ID NOs: 11-13 and 14-16, respectively.   
     
     
         55 . The method of  claim 53 , wherein:
 (a) the anti-IL-8 antibody comprises heavy and light chain variable region sequences set forth in SEQ ID NOs: 7 and 8, respectively; and   (b) the anti-PD-1 antibody comprises heavy and light chain variable region sequences set forth in SEQ ID NOs: 17 and 18, respectively.   
     
     
         56 . The method of  claim 53 , further comprising administering to the subject an effective amount of an anti-CTLA-4 antibody. 
     
     
         57 . The method of  claim 56 , wherein the anti-CTLA-4 antibody is selected from ipilimumab and tremelimumab. 
     
     
         58 . The method of  claim 56 , wherein the anti-CTLA-4 antibody is ipilimumab. 
     
     
         59 . The method of  claim 58 , wherein the anti-IL-8 antibody is administered at a fixed dose of (a) 2400 mg or 3600 mg once every two weeks or 14 days or (b) 3600 mg or 5000 mg once every three weeks or 21 days. 
     
     
         60 . The method of  claim 59 , wherein the anti-PD-1 antibody is administered once every three weeks or 21 days. 
     
     
         61 . The method of  claim 60 , wherein treatment includes administering the anti-IL-8 antibody and anti-PD-1 antibody in four-week cycles. 
     
     
         62 . The method of  claim 61 , wherein treatment includes administering the anti-IL-8 antibody and anti-PD-1 antibody for three to six cycles. 
     
     
         63 . The method of  claim 62 , further comprising subsequently administering to the subject an effective amount of the anti-IL-8 antibody and the anti-PD-1 antibody, wherein:
 (a) the anti-IL-8 antibody is administered at a fixed dose of 3600 mg once every two weeks or 14 days; and   (b) the anti-PD-1 antibody is administered at a fixed dose of 480 mg once every 4 weeks or 28 days.   
     
     
         64 . The method of  claim 53 , wherein:
 (a) the anti-IL-8 antibody comprises heavy and light chain variable region sequences set forth in SEQ ID NOs: 7 and 8, respectively, wherein the anti-IL-8 antibody is administered at a fixed dose of 3600 mg once every two weeks or 14 days;   (b) the anti-PD-1 antibody comprises heavy and light chain variable region sequences set forth in SEQ ID NOs: 17 and 18, respectively, wherein the anti-PD-1 antibody is administered once every three weeks or 21 days; and   further comprising administering to the subject an effective amount of an anti-CTLA-4 antibody, ipilimumab, and   wherein the treatment consists of three four-week cycles, followed by subsequently administering to the subject an effective amount of the anti-IL-8 antibody and the anti-PD-1 antibody, wherein:   (c) the anti-IL-8 antibody is administered at a fixed dose of 3600 mg once every two weeks or 14 days; and   (d) the anti-PD-1 antibody is administered at a fixed dose of 480 mg once every 4 weeks or 28 days.   
     
     
         65 . The method of  claim 53 , wherein baseline serum IL-8 level in the subject is (a)>10 pg/mL, (b) between 10 pg/mL and 100 pg/mL, (c) between 10 pg/mL and 50 pg/mL, (d) between 10 pg/mL and 30 pg/mL, or (e) between 10 pg/mL and 23 pg/mL. 
     
     
         66 . The method of  claim 53 , wherein the solid tumor has progressed or relapsed after anti-PD-1 or anti-PD-L1 therapy. 
     
     
         67 . The method of  claim 53 , wherein the anti-IL-8 antibody, or anti-IL8 antibody and anti-PD-1 antibody, are formulated for intravenous administration. 
     
     
         68 . The method of  claim 53 , wherein the anti-IL-8 antibody and anti-PD-1 antibody are formulated together or formulated separately. 
     
     
         69 . The method of  claim 53 , wherein the treatment produces at least one therapeutic effect chosen from a reduction in size of a tumor, reduction in number of metastatic lesions over time, complete response, partial response, and stable disease. 
     
     
         70 . The method of  claim 53 , wherein the solid tumor is associated with a cancer selected from the group consisting of: melanoma, non-small cell lung carcinoma, renal cell carcinoma, triple negative breast cancer, colorectal cancer, pancreatic ductal adenocarcinoma, prostate cancer, and hepatocellular carcinoma. 
     
     
         71 . The method of  claim 53 , wherein the tumor is metastatic. 
     
     
         72 . The method of  claim 53 , wherein the tumor is recurrent. 
     
     
         73 . The method of  claim 53 , wherein the tumor is unresectable. 
     
     
         74 . A kit for treating a solid tumor in a human subject, the kit comprising a dose of about 3600 mg to about 5000 mg of an anti-IL-8 antibody comprising CDR1, CDR2, and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO: 7, and CDR1, CDR2, and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO: 8, and a dose of an anti-PD-1 antibody comprising CDR1, CDR2, and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO: 17, and CDR1, CDR2, and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO: 18, and instructions for use.