Dosage Regimen for the Treatment of Cancer

Abstract

The present specification relates to AZD9833 for use in the treatment of cancer and methods of treatment of cancer involving administration of AZD9833 wherein, in each case, the AZD9833 is administered orally once daily at a dose between 25 mg and 450 mg. AZD9833 may be administered alone or its use may be in combination with an additional anti-cancer agent such as a CDK inhibitor, everolimus or an AKT inhibitor.

1 .- 28 . (canceled) 
     
     
         29 . A method of treating cancer in a human or animal patient in need of such treatment, comprising administering to the patient a compound, or a pharmaceutically acceptable salt thereof, once daily at a dose between 25 mg and 450 mg, wherein the compound is N-(1-(3-fluoropropyl)azetidin-3-yl)-6-((6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl)pyridin-3-amine. 
     
     
         30 . The method of  claim 29 , wherein the dose is selected from 25 mg, 75 mg, 150 mg, 300 mg, and 450 mg. 
     
     
         31 . The method of  claim 29 , wherein the compound is administered as a single dose unit or as multiple dose units. 
     
     
         32 . The method of  claim 31 , wherein the compound is administered as a single tablet. 
     
     
         33 . The method of  claim 29 , wherein the compound is administered in combination with a further anti-cancer therapy. 
     
     
         34 . The method of  claim 29 , wherein the compound is administered in combination with a CDK inhibitor. 
     
     
         35 . The method of  claim 34 , wherein the compound is administered in combination with palbociclib, ribociclib, abemaciclib, lerociclib, or trilaciclib. 
     
     
         36 . The method of  claim 34 , wherein the compound is administered in combination with palbociclib. 
     
     
         37 . The method of  claim 29 , wherein the compound is administered in combination with an mTOR inhibitor. 
     
     
         38 . The method of  claim 37 , wherein the compound is administered in combination with everolimus. 
     
     
         39 . The method of  claim 29 , wherein the cancer is selected from breast cancer and gynaecological cancer. 
     
     
         40 . The method of  claim 39 , wherein the cancer is ER-positive HER2-negative advanced breast cancer. 
     
     
         41 . The method of  claim 29 , wherein the compound is administered to a pre- or post-menopausal woman. 
     
     
         42 . The method of  claim 29 , wherein the cancer has previously been treated with one or more endocrine therapies and no more than two prior chemotherapies for ER-positive HER2-negative advanced breast cancer. 
     
     
         43 . The method of  claim 29 , wherein the compound is administered to a patient whose cancer is resistant to non-steroidal aromatase inhibitors. 
     
     
         44 . The method of  claim 29 , wherein the dose achieves a mean peak blood plasma concentration in the patient between 10 ng/mL and 1000 ng/mL. 
     
     
         45 . The method of  claim 29 , wherein the dose of the compound achieves a median terminal half-life in the patient between 8 hours and 14 hours. 
     
     
         46 . The method of  claim 29 , wherein the dose achieves a median terminal half-life in the patient of 12 hours. 
     
     
         47 . The method of  claim 29 , wherein the dose achieves an objective response rate in the patient between 10% and 20%. 
     
     
         48 . The method of  claim 29 , wherein the dose does not cause any serious side-effects in the patient. 
     
     
         49 . An oral pharmaceutical composition comprising between 25 mg and 450 mg of a compound, or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient; wherein the compound is N-(1-(3-fluoropropyl)azetidin-3-yl)-6-((6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl)pyridin-3-amine. 
     
     
         50 . The composition of  claim 49 , wherein the composition contains 25 mg, 75 mg, 150 mg, 300 mg, or 450 mg of the compound. 
     
     
         51 . The composition of  claim 50 , wherein the composition contains 75 mg of the compound. 
     
     
         52 . The composition of  claim 50 , wherein the composition contains 150 mg of the compound. 
     
     
         53 . The composition of  claim 49  in the form of a single tablet. 
     
     
         54 . A kit comprising:
 an oral pharmaceutical composition comprising from 25 mg to 450 mg of N-(1-(3-fluoropropyl)azetidin-3-yl)-6-((6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl)pyridin-3-amine, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient; and   instructions for the use of the composition in the treatment of cancer.   
     
     
         55 . The kit of  claim 54 , further comprising an additional anti-cancer agent for administration in combination with the composition.