Combination of a MCL-1 inhibitor and a taxane compound, uses and pharmaceutical compositions thereof

Patent metadata

Field	Value
Publication number	US-10765680-B2
Application number	US-201816475389-A
Country	US
Kind code	B2
Filing date	Jan 5, 2018
Priority date	Jan 6, 2017
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

A combination comprising a MCL-1 inhibitor and a taxane compound, and compositions and uses thereof.

First claim

The invention claimed is:

1. A combination comprising:
(a) an MCL-1 inhibitor which is (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno{2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl]methoxy}phenyl)propanoic acid or (2R)-2-{[5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno [2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid
or an addition salt thereof with a pharmaceutically acceptable acid or base,
and (b) a taxane compound which is paclitaxel or docetaxel.

2. The combination according to claim 1 , wherein the MCL-1 inhibitor is (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl]methoxy}phenyl)propanoic acid.

3. The combination according to claim 1 , wherein the MCL-1 inhibitor is (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno [2,3-d]pyrimidin-4-yl] oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid.

4. The combination according to claim 3 , wherein the (2R)-2-{[(5S a )-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno [2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy}phenyl)propanoic acid is present at a dosage from 25 mg to 1500 mg.

5. The combination according to claim 1 , further comprising one or more excipients.

6. A pharmaceutical composition comprising the combination according to claim 1 , in combination with one or more pharmaceutically acceptable excipients.

7. The pharmaceutical composition according to claim 6 , which is packaged for simultaneuous, sequential or separate administration.

8. A method of treating cancer in a subject in need thereof, comprising administration of an effective amount of the combination according to claim 1 , alone or in combination with one or more pharmaceutically acceptable excipients.

9. The method according to claim 8 , wherein the MCL-1 inhibitor and the taxane compound are administered in amounts which are jointly therapeutically effective for the treatment of cancer.

10. The method according to claim 8 , wherein the MCL-1 inhibitor and the taxane compound are administered in amounts which are synergistically effective for the treatment of cancer.

11. The method according to claim 8 , wherein the MCL-1 inhibitor and the taxane compound are administered in synergistically effective amounts which enable a reduction of the dose required for each compound in the treatment of cancer, whilst providing an efficacious cancer treatment, with eventually a reduction in side effects.

12. The method according to claim 8 , wherein the cancer is breast cancer.

13. The method according to claim 8 , wherein the cancer is lung cancer.

14. The method according to claim 8 , wherein the MCL-1 inhibitor is administered once a week.

15. The method according to claim 8 , wherein the MCL-1 inhibitor and the taxane compound are administered intravenously.

16. The method according to claim 8 , wherein the MCL-1 inhibitor is administered orally and the taxane compound is administered intravenously.

Assignees

• Servier Lab
• Novartis Ag
• Les Laboratories Servier

Inventors

• Porter Dale
• Halilovic Ensar
• Chanrion Maïa
• Maragno Ana Leticia
• Geneste Olivier
• Merino Delphine
• Whittle James
• Vaillant François
• Visvader Jane
• Lindeman Geoffrey
• Lessene Guillaume
• Marangoni Elisabetta

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/519 Primary

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/337 Primary

  having four-membered rings, e.g. taxol · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title