Compositions comprising coformulation of anti-pd-l1 and anti-ctla-4 antibodies

Abstract

Provided herein are compositions comprising coformulation of anti-PD-L1 and anti-CTLA-4 antibodies, or antigen-binding fragments thereof, and methods of making and using such compositions. In various aspects, stable coformulations of the anti-PD-L1 antibody durvalumab (MEDI4736) and the anti-CTLA-4 antibody tremelimumab are provided.

What is claimed is: 
     
         1 . A composition comprising durvalumab, or an antigen-binding fragment thereof, and tremelimumab, or an antigen-binding fragment thereof, wherein the concentration of durvalumab, or an antigen-binding fragment thereof, is about 18.7 mg/mL to about 44.4 mg/mL and wherein the concentration of tremelimumab, or an antigen-binding fragment thereof, is about 2.2 mg/mL to about 12.5 mg/mL. 
     
     
         2 . The composition of  claim 1 , wherein the concentration of durvalumab, or an antigen-binding fragment thereof, is about 18.7 mg/mL, 36.3 mg/mL, 40.0 mg/mL, 42.8 mg/mL, or 44.4 mg/mL. 
     
     
         3 . The composition of  claim 1  or  2 , wherein the concentration of tremelimumab, or an antigen-binding fragment thereof, is about 2.2 mg/mL, 2.9 mg/mL, 4.0 mg/mL, 5.5 mg/mL, or 12.5 mg/mL. 
     
     
         4 . The composition of any one of  claims 1 - 3 , wherein the combined concentration of durvalumab, or an antigen-binding fragment thereof, and tremelimumab, or an antigen-binding fragment thereof, is about 31.2 mg/mL to about 46.6 mg/mL. 
     
     
         5 . The composition of any one of  claims 1 - 3 , wherein the combined concentration of durvalumab, or an antigen-binding fragment thereof, and tremelimumab, or an antigen-binding fragment thereof, is about 31.2 mg/mL, 41.8 mg/mL, 44.0 mg/mL, 45.7 mg/mL, or 46.6 mg/mL. 
     
     
         6 . The composition of any one of  claims 1 - 5 , wherein the concentration ratio of durvalumab to tremelimumab is from about 15:10 to about 20:1. 
     
     
         7 . The composition of  claim 6 , wherein the concentration ratio of durvalumab to tremelimumab is about 20:1. 
     
     
         8 . The composition of any one of  claims 1 - 7 , further comprising Histidine, Histidine-HCl, or a combination thereof. 
     
     
         9 . The composition of  claim 8 , wherein the concentration of the Histidine, Histidine-HCl, or a combination thereof, is from about 20 mM to about 25 mM. 
     
     
         10 . The composition of any one of  claims 1 - 9 , further comprising trehalose dihydrate. 
     
     
         11 . The composition of  claim 10 , wherein the concentration of the trehalose dihydrate is from about 254 mM to about 269 mM. 
     
     
         12 . The composition of any one of  claims 1 - 11 , further comprising Ethylenediaminetetraacetic acid (EDTA). 
     
     
         13 . The composition of  claim 12 , wherein the concentration of EDTA is from about 0.03 mM to about 0.17 mM. 
     
     
         14 . The composition of any one of  claims 1 - 13 , further comprising polysorbate 80 (PS80). 
     
     
         15 . The composition of  claim 14 , wherein the concentration of polysorbate 80 is about 0.02 percent weight/volume (% w/v). 
     
     
         16 . The composition of any one of  claims 1 - 15 , having a pH of about 6.0. 
     
     
         17 . A pharmaceutical composition comprising or consisting of about 44.4 mg/mL durvalumab, or an antibody fragment thereof, about 2.2 mg/mL tremelimumab, or an antibody fragment thereof, about 25 mM Histidine/Histidine-HCl, about 269 mM Trehalose dehydrate, about 0.03 mM EDTA, and about 0.02% w/v PS80 at a pH of about 6.0. 
     
     
         18 . The composition of any one of  claims 1 - 17 , formulated for intravenous injection. 
     
     
         19 . A kit comprising the composition of any one of  claims 1 - 18 , and instructions for use in the method of any one of claims  35 - 37 . 
     
     
         20 . A kit comprising the composition of any one of  claims 1 - 18 , and instructions for use in the treatment of a solid tumor, cancer, lung cancer, or non-small cell lung cancer (NSCLC).