Pharmaceutical combination comprising lsz102 and ribociclib

Abstract

The present invention relates to a pharmaceutical combination comprising LSZ102 and ribociclib; 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 CDK4/6 inhibition is beneficial in, for example, the treatment of cancers.

What is claimed is: 
     
         1 . 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, in combination with 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The method of  claim 1  wherein the ER+ breast cancer is wild-type ER+ breast cancer. 
     
     
         3 . The method of  claim 1  wherein the ER+ breast cancer harbors ESR1 mutations. 
     
     
         4 . The method of  claim 3  wherein the ESR1 mutations are MCR7 expressing ESR1 mutations. 
     
     
         5 . The method of  claim 4  wherein the ESR1 mutations are selected from the group consisting of D538G, E380Q, Y537S, Y537N and Y537C. 
     
     
         6 . The method of  claim 5  wherein the ESR1 mutations are selected from D538G and Y537S. 
     
     
         7 . The method of  claim 1  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. 
     
     
         8 . The method of  claim 1  wherein 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide 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 500 mg per day, or 600 mg per day. 
     
     
         9 . The method of  claim 1  wherein 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide is administered orally at 600 mg for 21 days followed by 7 days off treatment.