Anti-B7-H1 and Anti-CTLA-4 Antibodies for Treating Non-Small Cell Lung Cancer

Abstract

Provided herein are methods of treating non-small cell lung cancers comprising administering an effective amount of MEDI4736 or an antigen-binding fragment thereof and tremelimumab or an antigen-binding fragment thereof.

1 - 27 . (canceled) 
     
     
         28 . A method of treating non-small cell lung carcinoma (NSCLC) in a human patient comprising administering MEDI4736 or an antigen-binding fragment thereof and tremelimumab or an antigen-binding fragment thereof to the patient, wherein the administrations increase progression-free survival. 
     
     
         29 . The method of  claim 28 , wherein the administrations result in an increase in progression-free survival as compared to the administration of either the MEDI4736 or an antigen-binding fragment thereof or the tremelimumab or an antigen-binding fragment thereof alone. 
     
     
         30 - 31 . (canceled) 
     
     
         32 . The method of  claim 28 , wherein the administrations result in a tumor response. 
     
     
         33 . The method of  claim 32 , wherein the administrations result in an increased tumor response as compared to the administration of either the MEDI4736 or an antigen-binding fragment thereof or the tremelimumab or an antigen-binding fragment thereof alone. 
     
     
         34 . The method of  claim 32 , wherein the tumor response can be detected by week 8 or week 33. 
     
     
         35 - 37 . (canceled) 
     
     
         38 . The method of  claim 28 , wherein the administrations increase overall survival. 
     
     
         39 . The method of  claim 38 , wherein the administrations result in an increase in overall survival as compared to the administration of either the MEDI4736 or an antigen-binding fragment thereof or the tremelimumab or an antigen-binding fragment thereof alone 
     
     
         40 . (canceled) 
     
     
         42 . The method of  claim 28 , wherein the administration of tremelimumab or an antigen-binding fragment thereof is repeated about every 12 weeks. 
     
     
         43 . The method of  claim 28 , wherein the administration of tremelimumab or an antigen-binding fragment thereof is administered about every 4 weeks for seven administrations and then every 12 weeks. 
     
     
         44 . The method of  claim 28 , wherein the administration reduces soluble PD-L1. 
     
     
         45 . The method of  claim 44 , wherein soluble PD-L1 is reduced by at least 65%, 80%, 90%, 95%, or 99%. 
     
     
         46 - 49 . (canceled) 
     
     
         50 . The method of  claim 28 , wherein the NSCLC is refractory to at least one chemotherapeutic agent. 
     
     
         51 . The method of  claim 50 , wherein the chemotherapeutic agent is Vemurafenib, Erlotinib, Afatinib, Cetuximab, Carboplatin, Bevacizumab, Erlotinib, Gefitinib, or Pemetrexed. 
     
     
         52 . The method of  claim 28 , wherein the patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 
     
     
         53 . The method of  claim 28 , wherein the patient is immunotherapy-naïve prior to the administration of MEDI4736 or antigen-binding fragment thereof and tremelimumab or antigen-binding fragment thereof. 
     
     
         54 . The method of  claim 28 , wherein the patient has received immunotherapy prior to the administration of MEDI4736 or antigen-binding fragment thereof and tremelimumab or antigen-binding fragment thereof. 
     
     
         55 . The method of  claim 28 , wherein the administration of MEDI4736 or an antigen-binding fragment thereof is by intravenous infusion and/or the administration of tremelimumab or an antigen-binding fragment thereof is by intravenous infusion. 
     
     
         56 . (canceled) 
     
     
         57 . The method of  claim 28 , wherein the MEDI4736 or an antigen-binding fragment thereof is MEDI4736 and wherein the tremelimumab or an antigen-binding fragment thereof is tremelimumab. 
     
     
         58 . The method of  claim 28 , wherein the administrations reduce tumor size by at least about 10%, 25%, or 50% relative to baseline. 
     
     
         59 . (canceled) 
     
     
         60 . The method of  claim 28 , wherein the human patient has locally advanced unresectable or metastatic NSCLC. 
     
     
         61 . The method of  claim 28 , wherein the NSCLC is squamous or non-squamous. 
     
     
         62 . The method of  claim 28 , wherein the NSCLC comprises a KRAS-mutation or an EGFR-mutation. 
     
     
         63 . The method of  claim 28 , wherein the NSCLC is PD-L1 positive or PD-L1 negative. 
     
     
         64 . (canceled) 
     
     
         65 . A method of treatment comprising administering MEDI4736 or an antigen-binding fragment thereof and tremelimumab or an antigen-binding fragment thereof to a patient identified as having a PD-L1− or PD-L1+ NSCLC. 
     
     
         66 - 101 . (canceled)