Pharmaceutical combination comprising lsz102 and alpelisib

Abstract

The present invention relates to a pharmaceutical combination comprising LSZ102 and alpelisib; pharmaceutical compositions comprising the same; and methods of using such combinations and compositions in the treatment or prevention of conditions in which degradation of estrogen receptors combined with PI3K inhibition is beneficial in, for example, the treatment of cancers.

1 - 17 . (canceled) 
     
     
         18 . A method for treating ER+ breast cancer comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical combination comprising (E)-3-(4-((2-(2-(1,1-difluoroethyl)-4-fluorophenyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid, or pharmaceutically acceptable salt thereof, and (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide, or a pharmaceutically acceptable salt thereof. 
     
     
         19 . The method according to  claim 18  wherein the ER+ breast cancer is wild-type ER+ breast cancer. 
     
     
         20 . The method according to  claim 18  wherein the ER+ breast cancer contains ESR1 mutations. 
     
     
         21 . The method of  claim 20  wherein the ESR1 mutations are MCRF7 expressing ESR1 mutations. 
     
     
         22 . The method of  claim 21  wherein the mutations are selected from the group consisting of D538G, E380Q, Y537S, Y537N and Y537C. 
     
     
         23 . The method of  claim 22  wherein the mutations are selected from D538G and Y537S. 
     
     
         24 . The method of  claim 18  wherein (E)-3-(4-((2-(2-(1,1-difluoroethyl)-4-fluorophenyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid is administered orally at a dose of about 100 mg per day, or 200 mg per day, or 300 mg per day, or 400 mg per day, or 450 mg per day, or 500 mg per day, or 600 mg per day, or 900 mg per day. 
     
     
         25 . The method of  claim 18  wherein (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide is administered orally at a dose of about 50 mg per day, or 100 mg per day, or 150 mg per day, or 200 mg per day, or 250 mg per day, or 300 mg per day, or 350 mg per day, or 400 mg per day, or 450 mg per day.