Methods of treating colorectal cancer

Abstract

This disclosure provides methods for treating a tumor derived from a colorectal cancer exhibiting a high degree of microsatellite instability in a subject comprising administering to the subject an anti-PD-1 antibody. In some embodiments, the method further comprises administering an anti-CTLA-4 antibody. In some embodiments, the colorectal cancer is rectal cancer, colon cancer, or any combination thereof.

1 . A method of treating a subject afflicted with a tumor derived from a colorectal cancer, comprising administering to the subject:
 (i) an anti-PD-1 antibody, and   (ii) an anti-CTLA-4 antibody;   wherein the tumor exhibits a high degree of microsatellite instability (“MSI-H”).   
     
     
         2 . The method of  claim 1 , wherein the tumor is a colon cancer or a rectal cancer. 
     
     
         3 . The method of  claim 1 , wherein the tumor exhibits one or more characteristics selected from the group consisting of:
 (a) the tumor comprises a germline alteration in at least two DNA mismatch repair genes (“MMR genes”);   (b) the tumor comprises a germline alteration in at least 30% of five or more MMR genes;   (c) at least one protein encoded by DNA MMR genes is not detected in the tumor; and   (d) any combination thereof.   
     
     
         4 . The method of  claim 3 , wherein the DNA MMR genes comprise MSH2, MLH1, MSH6, PMS2, PMS1, or any combination thereof. 
     
     
         5 . The method of  claim 1 , wherein:
 (i) the subject exhibits a progression-free survival of at least about one month after the administration, or   (ii) the subject exhibits an overall survival of at least about one month after the administration.   
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the anti-PD-1 antibody is nivolumab or pembrolizumab. 
     
     
         8 . The method of  claim 1 , wherein the anti-CTLA-4 antibody is administered at a dose ranging from at least about 0.1 mg/kg to at least about 10.0 mg/kg body weight once about every 1, 2, 3, or 4 weeks. 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the anti-CTLA-4 antibody is ipilimumab or tremelimumab. 
     
     
         11 . The method of  claim 1 , wherein the anti-PD-1 antibody is administered at a dose ranging from at least about 0.1 mg/kg to at least about 10.0 mg/kg body weight once about every 1, 2, 3 or 4 weeks. 
     
     
         12 . The method of  claim 1 , wherein:
 (i) the anti-PD-1 antibody is administered at a dose of about 1 mg/kg body weight and the anti-CTLA-4 antibody is administered at a dose of about 1 mg/kg body weight;   (ii) the anti-PD-1 antibody is administered at a dose of about 1 mg/kg body weight and the anti-CTLA-4 antibody is administered at a dose of about 3 mg/kg body weight;   (iii) the anti-PD-1 antibody is administered at a dose of about 3 mg/kg body weight and the anti-CTLA-4 antibody is administered at a dose of about 1 mg/kg body weight; or   (iv) the anti-PD-1 antibody is administered at a dose of about 3 mg/kg body weight and the anti-CTLA-4 antibody is administered at a dose of about 3 mg/kg body weight.   
     
     
         13 . The method of  claim 12 , wherein the administration of the anti-PD-1 antibody and the anti-CTLA-4 antibody is followed by an anti-PD-1 antibody monotherapy. 
     
     
         14 . (canceled) 
     
     
         15 . A kit for treating a patient afflicted with a tumor derived from colorectal cancer, wherein the tumor exhibits a high degree of microsatellite instability (“MSI-H”), the kit comprising:
 (a) a dosage ranging from 0.1 mg/kg to 10 mg/kg body weight of an anti-PD-1 antibody; 
 (b) a dosage ranging from 0.1 mg/kg to 10 mg/kg body weight of an anti-CTLA-4 antibody; and 
 (c) instructions for using the anti-PD-1 antibody and the anti-CTLA-4 antibody in the method of  claim 1 . 
 
     
     
         16 . The method of  claim 1 , wherein the anti-PD-1 antibody is administered at a dose of about 3 mg/kg body weight and the anti-CTLA-4 antibody is administered at a dose of about 1 mg/kg body weight once about every 3 weeks for a total of 12 weeks. 
     
     
         17 . The method of  claim 16 , wherein the administration of the anti-PD-1 antibody and the anti-CTLA-4 antibody is followed by an anti-PD-1 antibody monotherapy. 
     
     
         18 . The method of  claim 17 , wherein the anti-PD-1 antibody monotherapy is administered once about every 2 weeks. 
     
     
         19 . The method of  claim 17 , wherein the anti-PD-1 antibody monotherapy is administered at a dose of about 3 mg/kg once about every 2 weeks. 
     
     
         20 . The method of  claim 17 , wherein the anti-PD-1 antibody monotherapy is administered as a flat dose. 
     
     
         21 . The method of  claim 17 , wherein the anti-PD-1 antibody monotherapy is administered at a flat dose of about 240 mg once about every 2 weeks. 
     
     
         22 . The method of  claim 21 , wherein the anti-PD-1 antibody is nivolumab. 
     
     
         23 . The method of  claim 22 , wherein the anti-CTLA-4 antibody is ipilimumab.