Administration of NEDD8-activating enzyme inhibitor and chemotherapeutic agents

Patent metadata

Field	Value
Publication number	US-10786505-B2
Application number	US-201815980165-A
Country	US
Kind code	B2
Filing date	May 15, 2018
Priority date	May 14, 2013
Publication date	Sep 29, 2020
Grant date	Sep 29, 2020

Abstract

Disclosed are methods for the treatment of various solid tumors in patients in need of such treatment. The methods comprise administering to such a patient an NEDD8-activating enzyme (NAE) inhibitor such as ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]-pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate (MLN4924) or a pharmaceutically acceptable salt in combination with one or more chemotherapeutic agents. Also disclosed are medicaments for use in the treatment of various solid tumors.

First claim

What is claimed is:

1. A method of treating a solid tumor, comprising administering to a patient in need of such treatment a combination of: ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate or a pharmaceutically acceptable salt thereof; and
carboplatin;
wherein the solid tumor is lung cancer.

2. The method of claim 1 , wherein the ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-lylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate or a pharmaceutically acceptable salt thereof is administered on each of days 1, 3, and 5 of a 21 day schedule.

3. The method of claim 2 , wherein the amount of ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate or a pharmaceutically acceptable salt thereof administered on each of days 1, 3, and 5 of a 21 day schedule is less than or equal to 50 mg/m 2 .

4. The method of claim 1 , wherein the lung cancer is non-small cell lung cancer.

5. The method of claim 3 , wherein the amount of ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate or a pharmaceutically acceptable salt thereof administered on each of days 1, 3, and 5 of a 21 day schedule is less than or equal to 25 mg/m 2 .

6. The method of claim 3 , wherein the amount of ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate or a pharmaceutically acceptable salt thereof administered on each of days 1, 3, and 5 of a 21 day schedule is less than or equal to 20 mg/m 2 .

7. The method of claim 1 , wherein the carboplatin is administered on day 1 of a 21 day schedule.

8. The method of claim 1 , wherein a HCl salt of ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate is administered.

9. The method of claim 7 , wherein the amount of carboplatin administered on day 1 of a 21 day schedule is AUC 5 or AUC 6.

10. The method of claim 7 , wherein the amount of ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate or a pharmaceutically acceptable salt thereof administered on each of days 1, 3, and 5 of a 21 day schedule is less than or equal to 25 mg/m 2 ;
wherein the amount of carboplatin administered on day 1 of a 21 day schedule is AUC 5 or AUC 6.

11. The method of claim 10 , wherein a HCl salt of ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate is administered.

12. The method of claim 10 , wherein the solid tumor is lung cancer.

13. The method of claim 10 , wherein the lung cancer is non-small cell lung cancer.

Assignees

• Millennium Pharm Inc

Inventors

• Berger Allison
• Lightcap Eric S

Classifications

• A61K33/243

  Platinum; Compounds thereof · CPC title

• A61K31/282

  Platinum compounds · CPC title

• A61K31/555

  containing heavy metals, e.g. hemin, hematin, melarsoprol · CPC title

• A61K31/7068

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title

• A61K31/519 Primary

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