Checkpoint inhibitor and a whole cell mycobacterium for use in cancer therapy

Abstract

An immunomodulator for use in the treatment, reduction, inhibition or control of a neoplastic disease in a patient intended to undergo checkpoint inhibition therapy, selected from a cell, protein, peptide, antibody or antigen binding fragment thereof, directed against CTLA-4, PD-1, PD-L1 and combinations thereof, simultaneously, separately or sequentially with administration of the immunomodulator. The immunomodulator comprises a whole cell Mycobacterium, for example, M. vaccae or M. obuense.

We claim: 
     
         1 . A method for use in the treatment, reduction, inhibition or control of neoplasia, tumour and/or cancer in a subject, wherein said method comprises administering to the subject, (i) a checkpoint inhibitor comprising an antibody selected from MEDI-4736, MSB001078C, BMS-986016, MGA-271, MEDI-0680, or tremelimumab, or combinations thereof, and (ii) an immunomodulator, wherein said method results in enhanced therapeutic efficacy relative to administration of the checkpoint inhibitor or immunomodulator alone, wherein said immunomodulator comprises whole cell, non-pathogenic heat-killed  Mycobacterium  obuense and wherein said immunomodulator is administered simultaneously, separately or sequentially with administration of the checkpoint inhibitor. 
     
     
         2 . The method according to  claim 1 , wherein said checkpoint inhibitor comprises MSB001078C. 
     
     
         3 . The method according to  claim 1 , wherein said cancer is selected from prostate cancer, liver cancer, renal cancer, lung cancer, breast cancer, colorectal cancer, pancreatic cancer, brain cancer, hepatocellular cancer, lymphoma, leukaemia, gastric cancer, cervical cancer, ovarian cancer, thyroid cancer, melanoma, head and neck cancer, skin cancer or soft tissue sarcoma. 
     
     
         4 . The method according to  claim 3 , wherein said cancer is selected from melanoma, pancreatic, colorectal, prostate or ovarian cancer. 
     
     
         5 . The immunomodulator for use according to  claim 1 , wherein said cancer is metastatic. 
     
     
         6 . The method according to  claim 1 , wherein said whole cell, non-pathogenic heat-killed  Mycobacterium  obuense is the rough variant. 
     
     
         7 . The method according to  claim 6 , wherein said whole cell, non-pathogenic heat-killed  Mycobacterium  obuense and/or checkpoint inhibitor is administered via the parenteral, oral, sublingual, nasal or pulmonary route. 
     
     
         8 . The method according to  claim 7 , wherein the parenteral route is selected from subcutaneous, intradermal, subdermal, intraperitoneal, or intravenous. 
     
     
         9 . The method according to  claim 7 , wherein the parenteral route comprises intratumoural injection or administration adjacent to tumours or adjacent to lymph nodes. 
     
     
         10 . The method according to  claim 1 , wherein the amount of whole cell, non-pathogenic heat-killed  Mycobacterium  obuense administered per dose is from 10 7  to 10 9  cells, or preferably from 0.1 mg to 1 mg organisms. 
     
     
         11 . The method according to  claim 1 , wherein the enhanced therapeutic efficacy is measured by increased overall survival time. 
     
     
         12 . The method according to  claim 1 , wherein the enhanced therapeutic efficacy is measured by increased progression free survival. 
     
     
         13 . The method according to  claim 1 , wherein the enhanced therapeutic efficacy is measured by a decrease or stabilisation of tumour size. 
     
     
         14 . The method according to  claim 1 , wherein the enhanced therapeutic efficacy is measured by an improved overall response rate and/or increased quality of life.