Anti-pd-1 antibody in combination with an anti-cd30 antibody in cancer treatment

Abstract

This disclosure provides methods for treating a tumor in a subject comprising administering to the subject an anti-PD-1 antibody and an anti-CD30 antibody. In some embodiments, the tumor is derived from a lymphoma (e.g., a Hodgkin lymphoma or a non-Hodgkin lymphoma). In certain embodiments, the anti-CD30 antibody is an antibody-drug conjugate, e.g., brentuximab vedotin.

1 . A method of treating a human subject afflicted with a tumor derived from a non-Hodgkin lymphoma or a tumor derived from a Hodgkin lymphoma, comprising administering to the human subject a combination of:
 (a) an antibody or an antigen-binding portion thereof that binds specifically to a Programmed Death-1 receptor (PD-1) and inhibits PD-1 activity (“anti-PD-1 antibody”); and   (b) an antibody or an antigen-binding portion thereof that specifically binds to CD30 (“anti-CD30 antibody”).   
     
     
         2 . The method of  claim 1 , wherein (i) the non-Hodgkin lymphoma is relapsed or refractory non-Hodgkin lymphoma; (ii) the non-Hodgkin lymphoma is selected from diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), and any combination thereof (iii) the Hodgkin lymphoma is classical Hodgkin lymphoma (cHL); or (iv) the Hodgkin lymphoma is relapsed or refractory Hodgkin lymphoma, optionally relapsed HL after autologous stem cell transplant (ASCT) or relapsed HL in a human subject ineligible for ASCT. 
     
     
         3 . The method of  claim 1 , wherein the non-Hodgkin lymphoma is selected from the group consisting of diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), and any combination thereof. 
     
     
         4 . The method of  claim 1 , wherein the tumor comprises one or more cells that express CD30. 
     
     
         5 . The method of  claim 4 , wherein at least about 0.1%, at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, or at least about 80% of the tumor cells express CD30. 
     
     
         6 . The method of  claim 5 , wherein (i) the anti-CD30 antibody cross-competes for binding to CD30 with cAC10, (ii) the anti-CD30 antibody comprises cAC10, or (iii) the anti-CD30 antibody is an anti-CD30 antibody conjugated to a therapeutic agent, optionally comprising an anti-neoplastic agent, such as an anti-mitotic agent, or monomethyl auristatin E (MMAE), and further optionally comprising a linker, such as a cleavable linker, between the therapeutic agent and the CD30 antibody. 
     
     
         7 . The method of  claim 1 , wherein the anti-CD30 antibody is brentuximab vedotin. 
     
     
         8 . The method of  claim 1 , 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. 
     
     
         9 . The method of  claim 1 , 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 or 3 weeks; (ii) the anti-PD-1 antibody is administered at a dose of at least about 3 mg/kg body weight once about every 2 weeks; (iii) the anti-PD-1 antibody is administered at a dose of at least about 3 mg/kg body weight once about every 3 weeks; (iv) the anti-PD-1 antibody or antigen-binding portion thereof is administered at a flat dose, optionally, at least about 200 mg, at least about 220 mg, at least about 240 mg, at least about 260 mg, at least about 280 mg, at least about 300 mg, at least about 320 mg, at least about 340 mg, at least about 360 mg, at least about 380 mg, at least about 400 mg, at least about 420 mg, at least about 440 mg, at least about 460 mg, at least about 480 mg, at least about 500 mg, or at least about 550 mg administered about once every 1, 2, 3, or 4 weeks. 
     
     
         10 . The method of  claim 1 , wherein (i) the anti-CD30 antibody is administered at a dose ranging from at least about 0.1 mg/kg to at least about 180 mg/kg body weight once about every 1, 2 or 3 weeks; (ii) the anti-CD30 antibody is administered at a dose ranging from at least about 1.0 mg/kg to at least about 10 mg/kg body weight once about every 1, 2 or 3 weeks; (iii) the anti-CD30 antibody is administered at a dose of at least about 2 mg/kg body weight once about every 3 weeks; or (iv) the anti-CD30 antibody is administered at a dose of 1.8 mg/kg body weight once about every 3 weeks. 
     
     
         11 . The method of  claim 1 , wherein
 (a) the anti-CD30 antibody is administered to the human subject on day 1 of a first 21-day cycle and the anti-PD-1 antibody is administered to the human subject on day 8 of the first 21-day cycle; and   (b) optionally, a combination of the anti-CD30 antibody and the anti-PD-1 antibody is administered on day 1 of each of a second 21-day cycle, a third 21-day cycle, and a fourth 21-day cycle,   
       wherein the second 21-day cycle, the third 21-day cycle, and the fourth 21-day cycle follow in succession after the first 21-day cycle, and 
       wherein the anti-CD30 antibody is administered at a dose of about 1.8 mg/kg and the anti-PD-1 antibody is administered at a dose of about 3 mg/kg. 
     
     
         12 . The method of  claim 1 , wherein the anti-PD-1 antibody and the anti-CD30 antibody are administered sequentially. 
     
     
         13 . The method of  claim 1 , wherein the tumor comprises one or more cells that express PD-L1, PD-L2, or both PD-L1 and PD-L2. 
     
     
         14 . The method of  claim 1 , wherein the human 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. 
     
     
         15 . A kit comprising:
 (a) a dosage ranging from about 4 mg to about 500 mg of an anti-PD-1 antibody;   (b) a dosage ranging from about 0.1 mg to about 500 mg of an anti-CD30 antibody; and   (c) instructions for using the anti-PD-1 antibody and the anti-CD30 antibody according to the method of  claim 1 .   
     
     
         16 . A method of treating a human subject afflicted with a tumor derived from a Hodgkin lymphoma, comprising administering to the human subject a combination of:
 (a) an anti-PD-1 antibody; and   (b) an anti-CD30 antibody.   
     
     
         17 . The method of  claim 16 , wherein (i) the Hodgkin lymphoma is classical Hodgkin lymphoma (cHL); or (ii) the Hodgkin lymphoma is relapsed or refractory Hodgkin lymphoma, optionally relapsed HL after autologous stem cell transplant (ASCT) or relapsed HL in a human subject ineligible for ASCT. 
     
     
         18 . The method of  claim 16 , wherein the tumor comprises one or more cells that express CD30. 
     
     
         19 . The method of  claim 16 , wherein (i) the anti-CD30 antibody cross-competes for binding to CD30 with cAC10, (ii) the anti-CD30 antibody comprises cAC10, or (iii) the anti-CD30 antibody is an anti-CD30 antibody conjugated to a therapeutic agent, optionally comprising an anti-neoplastic agent, such as an anti-mitotic agent, or monomethyl auristatin E (MMAE), and further optionally comprising a linker, such as a cleavable linker, between the therapeutic agent and the anti-CD30 antibody. 
     
     
         20 . The method of  claim 16 , wherein the anti-CD30 antibody is brentuximab vedotin.