# US 2019/0167652 A1 · Pharmaceutical combination comprising lsz102 and alpelisib

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- Number: US 2019/0167652 A1
- Document ID: US20190167652A1
- Status: Published application
- Kind: A1
- Application number: 16/204,471
- Filed: 2018-11-29
- Published: 2019-06-06
- Earliest claimed: 2017-12-01
- Assignees: Novartis AG
- Applicants: Novartis AG
- Inventors: Tinya ABRAMS; Larry Alexander GAITHER
- Web page: https://patentgrep.com/patent/US20190167652A1

## CPC

- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/381: having five-membered rings
- A61P 35/00: Antineoplastic agents
- C07D 409/06: linked by a carbon chain containing only aliphatic carbon atoms
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## 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.

## Claims

### Claim 1

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.

### Claim 2 (depends on 1)

The combination of claim 1 wherein (E)-3-(4-((2-(1,1-difluoroethyl)-4-fluorophenyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid, or a 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, are administered separately, simultaneously or sequentially, in any order.

### Claim 3 (depends on 1, 2)

The pharmaceutical combination according to claim 1 or 2 which is for oral administration.

### Claim 4 (depends on 1, 2)

The pharmaceutical combination according to claim 1 or 2 wherein (E)-3-(4-((2-(2-(1,1-difluoroethyl)-4-fluorophenyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid is in an oral dose form.

### Claim 5 (depends on 1, 2)

The pharmaceutical combination according to claim 1 or 2 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 in a oral dose form.

### Claim 6

A pharmaceutical composition comprising the pharmaceutical combination according to any one of the preceding claims and at least one pharmaceutically acceptable carrier.

### Claim 7 (depends on 1, 2, 3, 4, 5, 6)

A pharmaceutical combination according to any one of claims 1 to 5 or the pharmaceutical composition according to claim 6 for use in the treatment of cancer.

### Claim 8 (depends on 7)

The pharmaceutical combination of claim 7 wherein the cancer is ER+ breast cancer.

### Claim 9 (depends on 1, 2, 3, 4, 5, 6)

Use of the pharmaceutical combination according to any one of claims 1 to 5 or the pharmaceutical composition according to claim 6 for the manufacture of a medicament for the treatment of cancer.

### Claim 10 (depends on 9)

The use of the pharmaceutical combination according to claim 9 wherein the cancer is ER+ breast cancer.

### Claim 11 (depends on 1, 2, 3, 4, 5, 6)

A method of treating wild-type ER+ breast cancer comprising administrating to a patient in need thereof a pharmaceutical combination according to any one of claims 1 to 5 or the pharmaceutical composition according to claim 6.

### Claim 12 (depends on 1, 2, 3, 4, 5, 6)

A method of treating ER+ breast cancer, wherein said ER+ breast cancer contains ESR1 mutations, comprising administrating to a patient in need thereof a pharmaceutical combination according to any one of claims 1 to 5 or the pharmaceutical composition according to claim 6.

### Claim 13 (depends on 12)

The method of claim 12 wherein the ESR1 mutation is an MCR7 expressing ESR1 mutation.

### Claim 14 (depends on 13)

The method of claim 13 wherein the mutations are selected from the group consisting of D538G, E380Q, Y537S, Y537N and Y537C.

### Claim 15 (depends on 14)

The method of claim 14 wherein the mutations are selected from D538G and Y537S.

### Claim 16 (depends on 11, 12)

The method of claim 11 or 12 wherein (E)-3-(4-((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.

### Claim 17 (depends on 14)

The method of claim 14 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.