Treatment of lung cancer using an anti-fucosyl-gm1 antibody

Abstract

This disclosure provides a method for treating a subject afflicted with a lung cancer, which method comprises administering to the subject a therapeutically effective amount of an antibody or an antigen-binding portion thereof that specifically binds to Fucosyl-GM1.

What is claimed is: 
     
         1 . A method for treating a subject afflicted with a lung cancer, comprising administering to the subject a therapeutically effective amount of a monoclonal antibody or an antigen-binding portion thereof that binds specifically to Fucosyl-GM1, wherein the antibody is administered at a dose ranging from 10 to 2000 mg once every 1, 2, 3 or 4 weeks. 
     
     
         2 . The method of  claim 1 , wherein the lung cancer is small cell lung cancer (SCLC). 
     
     
         3 . The method of  claim 1 , wherein the antibody cross-competes with BMS-986012 for binding to Fucosyl-GM1, and further wherein BMS-986012 comprises heavy and light chain variable regions comprising the sequences set forth in SEQ ID NOs: 3 and 4, respectively. 
     
     
         4 . The method of  claim 1 , wherein the antibody is a chimeric, humanized or human monoclonal antibody or a portion thereof. 
     
     
         5 . The method of  claim 4 , wherein the antibody comprises a human IgG1 or IgG4 heavy chain constant region. 
     
     
         6 . The method of  claim 3 , wherein the antibody or antigen-binding portion thereof comprises:
 (a) a heavy chain variable region CDR1 comprising SEQ ID NO: 5   (b) a heavy chain variable region CDR2 comprising SEQ ID NO: 6;   (c) a heavy chain variable region CDR3 comprising SEQ ID NO: 7;   (d) a light chain variable region CDR1 comprising SEQ ID NO: 8;   (e) a light chain variable region CDR2 comprising SEQ ID NO: 9; and   (f) a light chain variable region CDR3 comprising SEQ ID NO: 10.   
     
     
         7 . The method of  claim 6 , wherein the antibody or antigen-binding portion thereof comprises heavy and light chain variable regions comprising the sequences set forth in SEQ ID NOs: 3 and 4, respectively. 
     
     
         8 . The method of  claim 1 , wherein the antibody is non-fucosylated. 
     
     
         9 . The method of  claim 1 , wherein the antibody is administered at a dose ranging from 20 to 1000 mg once every 3 weeks. 
     
     
         10 . The method of  claim 1 , wherein the method comprises at least one treatment cycle of three weeks. 
     
     
         11 . The method of  claim 10 , wherein the method comprises at least four treatment cycles of three weeks. 
     
     
         12 . The method of  claim 11 , wherein the antibody is administered on Days 1, 22, 43, and 64. 
     
     
         13 . The method of  claim 1 , wherein the antibody is administered according to a dosing regimen selected from the group consisting of:
 (a) about 20 mg of the antibody every 3 weeks;   (b) about 70 mg of the antibody every 3 weeks;   (c) about 160 mg of the antibody every 3 weeks;   (d) about 400 mg of the antibody every 3 weeks; and   (e) about 1000 mg of the antibody every 3 weeks.   
     
     
         14 . The method of  claim 13 , wherein the antibody is administered according to a dosing regimen selected from the group consisting of:
 (a) 20 mg of the antibody every 3 weeks;   (b) 70 mg of the antibody every 3 weeks;   (c) 160 mg of the antibody every 3 weeks;   (d) 400 mg of the antibody every 3 weeks; and   (e) 1000 mg of the antibody every 3 weeks.   
     
     
         15 . The method of  claim 1 , wherein the antibody is formulated for intravenous administration. 
     
     
         16 . The method of  claim 1 , wherein the subject has previously received an initial anti-cancer therapy. 
     
     
         17 . The method of  claim 16 , where the subject has a relapsed or refractory lung cancer. 
     
     
         18 . The method of  claim 1 , wherein the method produces at least one therapeutic effect selected from a reduction in size of a tumor, reduction in number of metastatic lesions over time, complete response, partial response, and stable disease. 
     
     
         19 . The method of  claim 1 , wherein administration of the antibody is continued for as long as clinical benefit is observed or until unmanageable toxicity or disease progression occurs. 
     
     
         20 . A kit for treating a subject afflicted with a lung cancer, comprising:
 (a) a dosage ranging from 10 to 2000 mg of an anti-Fucosyl-GM1 antibody or an antigen-binding portion thereof; and   (b) instructions for using the antibody in the method of  claim 1 .