Compounds and methods for treating cancer

Abstract

The present application provides methods and compositions for treating cancer, for example, renal cell carcinoma, melanoma, ovarian, breast, prostate, colon, pancreatic, bladder, liver, lung, and thyroid cancer, and more particularly to using an inhibitor of a stearoyl-Coenzyme A desaturase 1 (SCD1) enzyme in combination with a checkpoint inhibitor to treat these disorders.

1 - 111 . (canceled) 
     
     
         112 . A method of treating cancer in a subject, the method comprising administering to the subject in need thereof:
 (i) a therapeutically effective amount of a compound of formula:   
       
         
           
           
               
               
           
         
         
           or a pharmaceutically acceptable salt thereof, and 
         
         (ii) a therapeutically effective amount of at least two checkpoint inhibitors independently selected from:
 an antibody of programmed cell death protein-1 (PD-1); 
 an antibody of programmed death-ligand-1 (PD-L1); 
 an antibody of programmed death-ligand-2 (PD-L2); 
 an antibody of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4); 
 an antibody of Lymphocyte-activation gene 3 (LAG-3); 
 an antibody of Cluster of Differentiation 47 (CD47); 
 an antibody of Signal regulatory protein α (SIRP α); 
 an antibody of T-cell immunoglobulin and mucin-domain containing molecule (TIM-3) or (TIM-1); 
 an antibody of V-domain immunoglobulin (Ig) suppressor of T cell activation (VISTA); and 
 a dual antibody of LAG-3 and PD-1. 
 
       
     
     
         113 . The method of  claim 112 , wherein the at least two checkpoint inhibitors are independently selected from: an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-PD-L2 antibody, an anti-CTLA-4 antibody, and an anti-TIM-3 antibody. 
     
     
         114 . The method of  claim 112 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered to the subject with two checkpoint inhibitors. 
     
     
         115 . The method of  claim 114 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered to the subject with an anti-CTLA-4 antibody and an anti-TIM-3 antibody. 
     
     
         116 . The method of  claim 114 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered to the subject with an anti-CTLA-4 antibody and an anti-PD-1 antibody. 
     
     
         117 . The method of  claim 114 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered to the subject with an anti-TIM-3 antibody and an anti-PD-1 antibody. 
     
     
         118 . The method of  claim 114 , wherein the two checkpoint inhibitors are independently selected from: pembrolizumab, nivolumab, atezolizumab, ipilimumab, and TSR-022. 
     
     
         119 . The method of  claim 112 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered with at least three checkpoint inhibitors. 
     
     
         120 . The method of  claim 119 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered with three checkpoint inhibitors. 
     
     
         121 . The method of  claim 120  wherein the compound, or a pharmaceutically acceptable salt thereof, is administered to the subject with an anti-CTLA-4 antibody, an anti-TIM-3 antibody, and an anti-PD-1 antibody. 
     
     
         122 . The method of  claim 120 , wherein the three checkpoint inhibitors are selected from: pembrolizumab, nivolumab, atezolizumab, ipilimumab, and TSR-022. 
     
     
         123 . The method of  claim 112 , wherein the compound, or a pharmaceutically acceptable salt thereof, and the at least two checkpoint inhibitors, are administered concurrently. 
     
     
         124 . The method of  claim 112 , wherein the compound, or a pharmaceutically acceptable salt thereof, and the at least two checkpoint inhibitors, are administered sequentially. 
     
     
         125 . The method of  claim 112 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered orally. 
     
     
         126 . The method of  claim 112 , wherein each checkpoint inhibitor is administered intravenously. 
     
     
         127 . The method of  claim 112 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered in an amount from about 200 mg/kg to about 250 mg/kg. 
     
     
         128 . The method of  claim 112 , wherein the cancer is selected from the group consisting of: a kidney cancer, a liver cancer, a breast cancer, a lung cancer, a pancreatic cancer, a bladder cancer, a colon cancer, a melanoma, a thyroid cancer, an ovarian cancer, and a prostate cancer.