Method of Treating Renal Cell Carcinoma Using N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, (2S)-hydroxybutanedioate

Abstract

The present disclosure relates to a method of treating advanced renal cell carcinoma (RCC) in human patients who have received prior anti-angiogenic therapy using CABOMETYX, a kinase inhibitor.

1 .- 102 . (canceled) 
     
     
         103 . A method of treating advanced renal cell carcinoma with high tumor burden in a patient who has received prior anti-angiogenic therapy, comprising administering to the patient an amount of cabozantinib or a pharmaceutically acceptable salt thereof. 
     
     
         104 . The method of  claim 103 , wherein the cabozantinib is administered as cabozantinib (S)-malate. 
     
     
         105 . The method of  claim 103 , wherein the prior antiangiogenic therapy is selected from the group consisting of axitinib, pazopanib, sorafenib, sunitinib, bevacizumab, interleukins, interferon-α, peginterferon, and a combination thereof. 
     
     
         106 . The method of  claim 103 , wherein the patient has a sum of target lesion diameter of at least 65 mm. 
     
     
         107 . The method of  claim 106 , wherein the advanced renal cell carcinoma has metastasized to sites selected from the group consisting of lung, liver, lymph node, bone, and kidney. 
     
     
         108 . The method of  claim 104 , wherein cabozantinib (S)-malate is administered as a tablet formulation containing 20, 40, or 60 mg of cabozantinib once daily. 
     
     
         109 . A method of treating advanced renal cell carcinoma with visceral metastases in a patient who has received prior anti-angiogenic therapy, comprising administering to the patient cabozantinib or a pharmaceutically acceptable salt thereof. 
     
     
         110 . The method of  claim 109 , wherein the cabozantinib is administered as cabozantinib (S)-malate. 
     
     
         111 . The method of  claim 109 , wherein the prior antiangiogenic therapy is selected from the group consisting of axitinib, pazopanib, sorafenib, sunitinib, bevacizumab, interleukins, interferon-α, and peginterferon. 
     
     
         112 . The method of  claim 110 , wherein cabozantinib (S)-malate is administered as a tablet formulation containing 20, 40, or 60 mg of cabozantinib. 
     
     
         113 . The method of  claim 112 , wherein the cabozantinib (S)-malate is administered once daily. 
     
     
         114 . A method of treating advanced renal cell carcinoma in a patient who has received prior anti-angiogenic therapy, comprising administering cabozantinib or a pharmaceutically acceptable salt thereof, wherein the prior anti-angiogenic therapy is selected from the group consisting of interleukins, interferon-α, and peginterferon. 
     
     
         115 . The method of  claim 114 , wherein cabozantinib is administered as cabozantinib (S)-malate salt. 
     
     
         116 . The method of  claim 115 , wherein the patient has high tumor burden. 
     
     
         117 . The method of  claim 115 , wherein cabozantinib (S)-malate is administered as a tablet formulation containing 20, 40, or 60 mg of cabozantinib. 
     
     
         118 . The method of  claim 117 , wherein cabozantinib (S)-malate is administered as a tablet formulation selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                     
                 
                     
                   Theoretical Quantity (mg/unit dose) 
                 
                 
                 
                 
                 
               
                     
                   20-mg 
                   40-mg 
                   60-mg 
                 
                   Ingredient 
                   Tablet* 
                   Tablet* 
                   Tablet* 
                 
                     
                 
                 
                 
                 
                 
               
                   Cabozantinib (S)-malate 
                   25.34 
                   50.69 
                   76.03 
                 
                   Microcrystalline Cellulose, PH-102 
                   31.08 
                   62.16 
                   93.24 
                 
                   Lactose Anhydrous, 60M 
                   15.54 
                   31.07 
                   46.61 
                 
                   Hydroxypropyl Cellulose, EXF 
                   2.400 
                   4.800 
                   7.200 
                 
                   Croscarmellose Sodium 
                   4.800 
                   9.600 
                   14.40 
                 
                   Colloidal Silicon Dioxide 
                   0.2400 
                   0.4800 
                   0.7200 
                 
                   Magnesium Stearate (Non-Bovine) 
                   0.6000 
                   1.200 
                   1.800 
                 
                   Opadry ® Yellow (03K92254) 
                   3.200 
                   6.400 
                   9.600 
                 
                   Total Tablet weight 
                   83.20 
                   166.4 
                   249.6 
                 
                     
                 
             
                
                
               
            
             
                
                
                
               
            
             
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         119 . The method of  claim 118 , wherein the cabozantinib (S)-malate is administered once daily.