Combination therapy with peptide epoxyketones

Abstract

The invention provides combination therapy, wherein one or more other therapeutic agents are administered agents are administered with peptide epoxyketones or a pharmaceutically acceptable salt thereof. Another aspect of the invention relates to treating cancer with a peptide epoxyketone administered in combination with another therapeutic agent.

1 - 43 . (canceled) 
     
     
         44 . A method for treating multiple myeloma, the method comprising administering to a patient, a combination therapy comprising (1) a peptide epoxyketone proteasome inhibitor having the structure of 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof; and (2) one or more therapeutic agents; wherein the one or more therapeutic agents comprises lenalidomide and dexamethasone. 
       
     
     
         45 . The method of  claim 44 , wherein the peptide epoxyketone proteasome inhibitor is administered as a pharmaceutical composition including a cyclodextrin and optionally a buffer. 
     
     
         46 . The method of  claim 44 , wherein the peptide epoxyketone proteasome inhibitor and the one or more other therapeutic agents are administered within about 5 minutes to within about 48 hours of one another. 
     
     
         47 . The method of  claim 44 , wherein the peptide epoxyketone proteasome inhibitor is present in an amount of at least 15 mg/m 2  and the lenalidomide is present in an amount of at least 20 mg. 
     
     
         48 . The method of  claim 44 , wherein the multiple myeloma is relapsed or refractory multiple myeloma. 
     
     
         49 . The method of  claim 44 , wherein the lenalidomide is administered in a dosage amount of at least 10 mg. 
     
     
         50 . A method for treating multiple myeloma, consisting essentially of administering to a patient, in combination, (1) a peptide epoxyketone proteasome inhibitor, or a pharmaceutically acceptable salt thereof; (2) lenalidomide, and (3) dexamethasone;
 wherein the peptide epoxyketone proteasome inhibitor has the following structure:   
       
         
           
           
               
               
           
         
       
       and
 the efficacy shown by administering (1) and (2) in combination is greater than the efficacy shown by administering either of (1) or (2) alone. 
 
     
     
         51 . The method of  claim 50 , wherein the efficacy shown by administering (1) and (2) in combination is synergistically greater than the efficacy shown by administering either of (1) or (2) alone. 
     
     
         52 . The method of  claim 50 , wherein the peptide epoxyketone proteasome inhibitor is administered as a pharmaceutical composition including a cyclodextrin and optionally a buffer. 
     
     
         53 . The method of  claim 51 , wherein the peptide epoxyketone proteasome inhibitor is administered as a pharmaceutical composition including a cyclodextrin and optionally a buffer. 
     
     
         54 . The method of  claim 50 , wherein the peptide epoxyketone proteasome inhibitor and lenalidomide are administered within about 5 minutes to within about 48 hours of one another. 
     
     
         55 . The method of  claim 50 , wherein the peptide epoxyketone proteasome inhibitor, lenalidomide and dexamethasone are administered within about 5 minutes to within about 48 hours of one another.