Combination of anti-lag-3 antibodies and anti-pd-1 antibodies to treat tumors

Abstract

Provided are methods for clinical treatment of tumors (e.g., advanced solid tumors) using an anti-LAG-3 antibody in combination with an anti-PD-1 antibody.

1 - 20 . (canceled) 
     
     
         21 . A kit for treating a solid tumor in a human patient, the kit comprising:
 (a) an 80 mg dose of an anti-LAG-3 antibody comprising CDR1, CDR2 and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO:3, and CDR1, CDR2 and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO:5;   (b) a 240 mg 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: 19, and CDR1, CDR2 and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO:21; and   (c) instructions for using the anti-LAG-3 antibody and anti-PD-1 antibody in a method for treating a solid tumor.   
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . The kit of  claim 21 , wherein the anti-PD-1 and anti-LAG-3 antibodies are formulated for intravenous administration. 
     
     
         25 . The kit of  claim 21 , wherein the anti-PD-1 and anti-LAG-3 antibodies are formulated together. 
     
     
         26 . The kit of  claim 21 , wherein the anti-PD-1 and anti-LAG-3 antibodies are formulated separately. 
     
     
         27 . The kit of  claim 21 , wherein the solid tumor is chosen from melanoma, non-small cell lung cancer (NSCLC), human papilloma virus (HPV)-related tumor, and gastric adenocarcinoma. 
     
     
         28 . The kit of  claim 21 , wherein the anti-LAG-3 antibody comprises
 (a) a heavy chain variable region CDR1 comprising the sequence set forth in SEQ ID NO:7;   (b) a heavy chain variable region CDR2 comprising the sequence set forth in SEQ ID NO:8;   (c) a heavy chain variable region CDR3 comprising the sequence set forth in SEQ ID NO:9;   (d) a light chain variable region CDR1 comprising the sequence set forth in SEQ ID NO:10;   (e) a light chain variable region CDR2 comprising the sequence set forth in SEQ ID NO:11; and   (f) a light chain variable region CDR3 comprising the sequence set forth in SEQ ID NO:12.   
     
     
         29 . The kit of  claim 21 , wherein the anti-LAG-3 antibody comprises heavy and light chain variable regions comprising the sequences set forth in SEQ ID NOs:3 and 5, respectively. 
     
     
         30 . The kit of  claim 21 , wherein the anti-LAG-3 antibody comprises heavy and light chains comprising the sequences set forth in SEQ ID NOs: 1 and 2, respectively. 
     
     
         31 . The kit of  claim 21 , wherein the anti-PD-1 antibody comprises
 (a) a heavy chain variable region CDR1 comprising the sequence set forth in SEQ ID NO:23;   (b) a heavy chain variable region CDR2 comprising the sequence set forth in SEQ ID NO:24;   (c) a heavy chain variable region CDR3 comprising the sequence set forth in SEQ ID NO:25;   (d) a light chain variable region CDR1 comprising the sequence set forth in SEQ ID NO:26;   (e) a light chain variable region CDR2 comprising the sequence set forth in SEQ ID NO:27; and   (f) a light chain variable region CDR3 comprising the sequence set forth in SEQ ID NO:28.   
     
     
         32 . The kit of  claim 21 , wherein the anti-PD-1 antibody comprises heavy and light chain variable regions comprising the sequences set forth in SEQ ID NOs: 19 and 21, respectively. 
     
     
         33 . The kit of  claim 21 , wherein the anti-PD-1 antibody comprises heavy and light chains comprising the sequences as set forth in SEQ ID NOs: 17 and 18, respectively. 
     
     
         34 . The kit of  claim 21 , wherein the anti-LAG-3 antibody and/or anti-PD-1 antibody is a full-length antibody. 
     
     
         35 . The kit of  claim 21 , wherein the anti-LAG-3 antibody has a S228P mutation 
     
     
         36 . The kit of  claim 21 , wherein the patient has been previously treated with anti-PD-1 or anti-PD-L1 antibody therapy. 
     
     
         37 . The kit of  claim 21 , further comprising a dose of an anti-CTLA-4 antibody. 
     
     
         38 . The kit of  claim 37 , wherein the anti-CTLA-4 antibody is ipilimumab.