Combination therapies

Abstract

Provided herein are pharmaceutical compositions comprising a phosphatidylinositol 3-kinase inhibitor, or pharmaceutically acceptable form thereof, in combination with a second agent, or a pharmaceutically acceptable form thereof, wherein the second agent is chosen from one or more of 1) a checkpoint modulator, 2) an XPO1 inhibitor, 3) an anti-CD19 antibody, 4) a TLR agonist, 5) a STING agonist, or 6) a Flt3 ligand, or a combination thereof. Also provided herein are methods of treatment comprising administration of the compositions, and uses of the compositions, e.g., for treatment of cancer.

1 . A method of treating, managing, or preventing a cancer in a subject comprising administering to the subject a therapeutically effective amount of a PI3K inhibitor in combination with a second therapeutic agent, wherein the second therapeutic agent is 1) a checkpoint modulator, 2) an XPO1 inhibitor, 3) an anti-CD 19 antibody, 4) a TLR agonist, 5) a STING agonist, or 6) a Flt3 ligand, or a combination thereof. 
     
     
         2 . The method of  claim 1 , wherein the PI3K-inhibitor is a PI3K delta/gamma dual inhibitor. 
     
     
         3 . The method of  claim 1 , wherein the PI3K-inhibitor is Compound 1 of the following structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable form thereof. 
     
     
         4 . The method of  claim 1 , wherein the PI3K-inhibitor is a PI3K delta inhibitor. 
     
     
         5 . The method of  claim 1 , wherein the PI3K-inhibitor is Idelalisib of the following structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable form thereof. 
     
     
         6 . The method of  claim 1 , wherein second therapeutic agent is a checkpoint modulator. 
     
     
         7 . The method of  claim 6 , wherein the checkpoint modulator is a modulator of CTLA-4, CD 80, CD86, PD-1, PD-L1, PD-L2, LAG-3, Galectin-3, BTLA, TIM3, GAL9, B7-H1, B7-H3, B7-H4, TIGIT/Vstm3/WUCAM/VSIG9, VISTA, GITR, HVEM, OX40, CD27, CD28, CD137, CGEN-15001T, CGEN-15022, CGEN-15027, CGEN-15049, CGEN-15052, or CGEN-15092. 
     
     
         8 . The method of  claim 6 , wherein the checkpoint modulator is a PD-1 inhibitor. 
     
     
         9 . The method of  claim 6 , wherein the checkpoint modulator is an anti-PD-1 antibody. 
     
     
         10 . The method of  claim 9 , wherein the anti-PD-1 antibody is Nivolumab, Pembrolizumab, Pidilizumab, AMP-514, or AMP-224, or a combination thereof. 
     
     
         11 . The method of  claim 10 , wherein the anti-PD-1 antibody is Nivolumab. 
     
     
         12 . The method of  claim 10 , wherein the anti-PD-1 antibody is Pembrolizumab. 
     
     
         13 . The method of  claim 6 , wherein the checkpoint modulator is an anti-PD-L1 antibody. 
     
     
         14 . The method of  claim 13 , wherein the anti-PD-L1 antibody is M-DX-1105, YW243.55.S70, MDPL3280A, MSB0010718C, or durvalumab, or a combination thereof. 
     
     
         15 . The method of  claim 6 , wherein the checkpoint modulator is an anti-CTLA-4 antibody. 
     
     
         16 . The method of  claim 15 , wherein the an anti-CTLA-4 antibody is Tremelimumab or Ipilimumab, or a combination thereof. 
     
     
         17 . The method of  claim 16 , wherein the an anti-CTLA-4 antibody is Tremelimumab. 
     
     
         18 . The method of  claim 16 , wherein the an anti-CTLA-4 antibody is Ipilimumab. 
     
     
         19 . The method of  claim 6 , wherein the checkpoint modulator is a LAG-3 inhibitor. 
     
     
         20 . The method of  claim 6 , wherein the checkpoint modulator is a TIM3 inhibitor. 
     
     
         21 - 82 . (canceled)