Anti-pd-1 antibody for use in a method of treatment of recurrent small cell lung cancer

Abstract

This disclosure provides a method for treating a subject afflicted with a tumor derived from a small cell lung cancer, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity or the combination of (a) an antibody or an antigen-binding portion thereof that specifically binds to a PD-1 receptor and inhibits PD-1 activity; and (b) an antibody or an antigen-binding portion thereof that specifically binds to a Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) and inhibits CTLA-4 activity.

What is claimed is: 
     
         1 . An antibody or an antigen-binding portion thereof that binds specifically to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity (“anti-PD-1 antibody”) for use in a method of treating a subject afflicted with a tumor derived from a small cell lung cancer (SCLC), wherein the subject is administered the anti-PD-1 antibody in combination with an antibody or an antigen-binding portion thereof that binds specifically to Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) and inhibits CTLA-4 activity (“anti-CTLA-4 antibody”). 
     
     
         2 . The anti-PD-1 antibody for use according to  claim 1 , wherein the SCLC comprises a small cell carcinoma, a combined small cell carcinoma, or a recurrent SCLC. 
     
     
         3 . The anti-PD-1 antibody for use according to  claim 1  or  2 , wherein at least one, at least two, at least three, at least four, or at least five previous lines of therapy were administered to treat the tumor. 
     
     
         4 . The anti-PD-1 antibody for use according to  claim 3 , wherein the previous line of therapy comprises a chemotherapy, optionally a platinum-based therapy that preferably comprises a platinum-based antineoplastic selected from the group consisting of cisplatin, carboplatin, oxaliplatin, nedaplatin, triplatin tetranitrate, phenanthriplatin, picoplatin, satraplatin, and any combination thereof. 
     
     
         5 . The anti-PD-1 antibody for use according to any one of  claims 1  to  4 , wherein (i) the anti-PD-1 antibody cross-competes with nivolumab for binding to human PD-1; (ii) the anti-PD-1 antibody binds to the same epitope as nivolumab; (iii) the anti-PD-1 antibody is nivolumab; or (iv) the anti-PD-1 antibody is pembrolizumab. 
     
     
         6 . The anti-PD-1 antibody for use according to any one of  claims 1  to  5 , wherein (i) the anti-CTLA-4 antibody cross-competes with ipilimumab for binding to human CTLA-4; (ii) the anti-CTLA-4 antibody is ipilimumab; or (iii) the anti-CTLA-4 antibody is tremelimumab. 
     
     
         7 . The anti-PD-1 antibody for use according to any one of  claims 1  to  6 , wherein (i) 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; (ii) the anti-PD-1 antibody is administered at a dose of about 1 mg/kg or about 3 mg/kg body weight; (iii) the anti-PD-1 antibody is administered at a flat dose, optionally at least about 200, at least about 220, at least about 240, at least about 260, at least about 280, at least about 300, at least about 320, at least about 340, at least about 360, at least about 380, at least about 400, at least about 420, at least about 440, at least about 460, at least about 480, at least about 500 or at least about 550 mg, about once every 1, 2, 3 or 4 weeks; (iv) the anti-PD-1 antibody is administered once about every 2 weeks; or (v) the anti-PD-1 antibody is administered once about every 3 weeks. 
     
     
         8 . The anti-PD-1 antibody for use according to any one of  claims 1  to  7 , wherein (i) 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; (ii) the anti-CTLA-4 is administered at a dose of about 1 mg/kg or about 3 mg/kg body weight; (iii) the anti-CTLA-4 antibody is administered once about every 2 weeks; or (iv) the anti-CTLA-4 antibody is administered once about every 3 weeks. 
     
     
         9 . The anti-PD-1 antibody for use according to  claim 8 , wherein (i) the anti-PD-1 antibody is administered at a dose of about 3 mg/kg body weight once about every 3 weeks and the anti-CTLA-4 antibody is administered at a dose of about 1 mg/kg body weight once about every 3 weeks; (ii) the anti-PD-1 antibody is administered at a dose of about 1 mg/kg body weight once about every 3 weeks and the anti-CTLA-4 antibody is administered at a dose of about 3 mg/kg body weight once about every 3 weeks; or (iii) the anti-PD-1 antibody is administered at a dose of about 1 mg/kg body weight once about every 3 weeks and the anti-CTLA-4 antibody is administered at a dose of about 1 mg/kg body weight once about every 3 weeks. 
     
     
         10 . The anti-PD-1 antibody for use according to  claim 9 , wherein the administration of the anti-PD-1 antibody and the anti-CTLA-4 antibody was repeated four times (4 cycles). 
     
     
         11 . The anti-PD-1 antibody for use according to any one of  claims 1  to  10 , wherein the subject is further treated with an anti-PD-1 antibody monotherapy following the treatment in  claims 1  to  10 . 
     
     
         12 . The anti-PD-1 antibody for use according to any one of  claims 1  to  11 , wherein the subject exhibits progression-free survival of at least about one month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about one year, at least about eighteen months, at least about two years, at least about three years, at least about four years, or at least about five years after the initial administration. 
     
     
         13 . The anti-PD-1 antibody for use according to any one of  claims 1  to  12 , wherein the subject has a tumor that has ≥1% PD-L1 expression. 
     
     
         14 . The anti-PD-1 antibody for use according to any one of  claims 1  to  13 , wherein the subject has a tumor that has ≥5% PD-L1 expression. 
     
     
         15 . A kit comprising:
 (a) a dosage ranging from about 4 mg to about 500 mg of an antibody or an antigen-binding portion thereof that binds specifically to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity (“an anti-PD-1 antibody”);   (b) a dosage ranging from about 4 mg to about 500 mg of an antibody or an antigen-binding portion thereof that binds specifically to Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) and inhibits CTLA-4 activity (“a CTLA-4 antibody”); and   (c) instructions for using the PD-1 antibody and the CTLA-4 antibody according to any one of  claims 1  to  14 .