Duocarmycin adcs showing improved in vivo antitumor activity

Abstract

The present invention relates to duocarmycin-containing antibody-drug conjugates (ADCs) for use in the treatment of human solid tumours and haematological malignancies expressing HER2, in particular breast cancer, gastric cancer, bladder cancer, ovarian cancer, lung cancer, prostate cancer, pancreatic cancer, colorectal cancer, head and neck squamous cell cancer or osteosarcoma, and acute lymphoblastic leukaemia. In particular, the present invention relates to duocarmycin-containing ADCs for use in the treatment of human solid tumours with HER2 IHC 2+ or 1+ and HER2 FISH negative tissue status. Advantageously, the present invention relates to duocarmycin-containing ADCs for use in the treatment of triple negative breast cancer (TNBC).

1 - 15 . (canceled) 
     
     
         16 . A compound having the structure 
       
         
           
           
               
               
           
         
       
       wherein 2.5-2.9 represents an average DAR for the compound. 
     
     
         17 . The compound of  claim 16 , wherein the average DAR for the compound is from 2.6 to 2.9. 
     
     
         18 . A pharmaceutical composition, comprising the compound of  claim 16  and one or more pharmaceutically acceptable excipients. 
     
     
         19 . The pharmaceutical composition of  claim 18  in the form of a lyophilized powder or a frozen solution. 
     
     
         20 . The pharmaceutical composition of  claim 18 , further comprising one or more of a therapeutic antibody or a chemotherapeutic agent, or a combination thereof. 
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein the therapeutic antibody is pertuzumab and the chemotherapeutic agent is a taxane or an anthracycline. 
     
     
         22 . The pharmaceutical composition of  claim 21 , wherein the taxane is docetaxel or paclitaxel, and the anthracycline is doxorubicin, epirubicin, daunorubicin or valrubicin. 
     
     
         23 . A pharmaceutical composition for intravenous infusion, comprising a therapeutically effective amount of a compound having the structure 
       
         
           
           
               
               
           
         
       
       wherein 2.5-2.9 represents an average DAR for the compound, and one or more pharmaceutically acceptable excipients. 
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein the average DAR for the compound is from 2.6 to 2.9. 
     
     
         25 . The pharmaceutical composition of  claim 23  in the form of a lyophilized powder or a frozen solution.