Fgfr/pd-1 combination therapy for the treatment of cancer

Abstract

Provided herein are combination therapies for the treatment of cancer. In particular, the disclosed methods are directed to treatment of cancer in a patient comprising administering an antibody that blocks the interaction between PD-1 and PD-L1 and an FGFR inhibitor, wherein the antibody that blocks the interaction between PD-1 and PD-L1 and the FGFR inhibitor are administered if one or more FGFR variants are present in a biological sample from the patient.

1 . A method of treating cancer in a patient, comprising:
 administering to the patient a pharmaceutically effective amount of an antibody that blocks the interaction between PD-1 and PD-L1 and a pharmaceutically effective amount of an FGFR inhibitor, wherein the antibody that blocks the interaction between PD-1 and PD-L1 and the FGFR inhibitor are administered if one or more FGFR variants are present in a biological sample from the patient.   
     
     
         2 . The method of  claim 1 , further comprising evaluating the presence of one or more FGFR variants in the biological sample before the administering step. 
     
     
         3 . The method of  claim 1 , further comprising evaluating PD-L1 expression in a biological sample. 
     
     
         4 . The method of  claim 3 , wherein the biological sample for the one or more FGFR variants and the PD-L1 is the same biological sample. 
     
     
         5 . The method of  claim 3 , wherein the biological sample for the one or more FGFR variants is different from the biological sample for PD-L1 expression. 
     
     
         6 . The method of  claim 1 , wherein the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample, or any combination thereof. 
     
     
         7 . The method of  claim 1 , wherein the administering step is performed if PD-L1 expression is low in the biological sample. 
     
     
         8 . The method of  claim 1 , wherein the cancer is lung cancer, bladder cancer, gastric cancer, breast cancer, ovarian cancer, head and neck cancer, esophageal cancer, glioblastoma, or any combination thereof. 
     
     
         9 . The method of  claim 8 , wherein the lung cancer is non-small cell lung cancer (NSCLC) adenocarcinoma, NSCLC squamous cell carcinoma, small cell lung cancer, or any combination thereof. 
     
     
         10 . The method of  claim 1 , wherein the one or more FGFR variants comprise an FGFR mutation, an FGFR amplification, an FGFR fusion gene, or a combination thereof. 
     
     
         11 . The method of  claim 10 , wherein the FGFR fusion gene is FGFR2:AFF3; FGFR2:BICC1; FGFR2:CASP7; FGFR2:CCDC6; FGFR2:OFD1; FGFR3:BAIAP2L1; FGFR3:TACC3-Intron; FGFR3:TACC3V1; FGFR3:TACC3V3; or a combination thereof. 
     
     
         12 . The method of  claim 1 , wherein the antibody that blocks the interaction between PD-1 and PD-L1 is an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination thereof. 
     
     
         13 . The method of  claim 1 , wherein the FGFR inhibitor is the compound of formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         14 . A method of treating cancer in a patient comprising:
 administering to the patient a pharmaceutically effective amount of an antibody that blocks the interaction between PD-1 and PD-L1;   monitoring the efficacy of the antibody; and   if the antibody is not efficacious,
 evaluating a biological sample from the patient for a presence of one or more FGFR variants; and 
 administering to the patient a pharmaceutically effective amount of an FGFR inhibitor if the one or more FGFR variants are present in the sample. 
   
     
     
         15 . The method of  claim 14 , wherein the evaluating step further comprises measuring an expression level of PD-L1 in a biological sample and wherein the second administering step comprises administering the FGFR inhibitor if the expression level of PD-L1 is low. 
     
     
         16 . The method of  claim 15 , wherein the biological sample for the one or more FGFR variants and the PD-L1 is the same biological sample. 
     
     
         17 . The method of  claim 15 , wherein the biological sample for the one or more FGFR variants is different from the biological sample for PD-L1 expression. 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 16 , wherein the cancer is lung cancer, bladder cancer, gastric cancer, breast cancer, ovarian cancer, head and neck cancer, esophageal cancer, glioblastoma, or any combination thereof. 
     
     
         20 . The method of  claim 19 , wherein the lung cancer is non-small cell lung cancer (NSCLC) adenocarcinoma, NSCLC squamous cell carcinoma, small cell lung cancer, or any combination thereof. 
     
     
         21 - 23 . (canceled) 
     
     
         24 . The method of  claim 16 , wherein the FGFR inhibitor is the compound of formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.