Method of treating cancer with a combination of MER tyrosine kinase inhibitor and an epidermal growth factor receptor (EGFR) inhibitor

Patent metadata

Field	Value
Publication number	US-10709708-B2
Application number	US-201715462299-A
Country	US
Kind code	B2
Filing date	Mar 17, 2017
Priority date	Mar 17, 2016
Publication date	Jul 14, 2020
Grant date	Jul 14, 2020

Abstract

The invention provides combinations comprising a MERTK inhibitor, or a pharmaceutically acceptable salt thereof, and an EGFR inhibitor and methods of use thereof, including methods of treating disorders such as cancer.

First claim

That which is claimed:

1. A method of treating tumors, wherein said tumors comprise non-small cell lung cancer tumors in a mammalian subject in need thereof, comprising:
concurrently administering to said subject a MER tyrosine kinase inhibitor and an Epidermal Growth Factor Receptor (EGFR) inhibitor, wherein said MER tyrosine kinase inhibitor is

or a pharmaceutically acceptable salt thereof, and said EGFR inhibitor is Osimertinib (AZD-9291), and wherein said MER tyrosine kinase inhibitor is administered to said subject in an amount effective to enhance the efficacy of said EGFR inhibitor in treating said tumors.

2. The method of claim 1 , wherein said tumors comprise malignant primary tumors.

3. The method of claim 1 , wherein said tumors comprise metastatic secondary tumors.

4. The method of claim 1 , wherein said tumors comprise metastatic non-small cell lung cancer tumors in the brain.

5. The method of claim 1 , wherein:
cells of said tumors over-express wild-type EGFR, and/or
cells of said tumors express a mutant EGFR.

6. The method of claim 5 , wherein said mutant EGFR is selected from the group consisting of the L858R activating mutant, the Exon 19 deletion activating mutant, the ΔE746-A750 activating mutant, the G719C activating mutant, the G719S activating mutant, the G719A activating mutant, the T790M resistance mutant, the C797S resistance mutant, and the D761Y resistance mutant.

7. The method of claim 1 , wherein said first active compound and said EGFR inhibitor are administered in a synergistic effective amount.

8. The method of claim 1 , wherein said subject is human.

9. The method of claim 1 , wherein said method results in one or more of: (a) inhibition of tumor growth; (b) reduction in tumor size; (c) reduction in the number of tumors, and (d) decreased tumor burden in the subject.

Assignees

• Univ Emory
• Univ North Carolina Chapel Hill

Inventors

• Yan Dan
• Earp Iii H Shelton
• Deryckere Deborah Ann
• Graham Douglas Kim
• Wan Jing

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K31/506 Primary

  not condensed and containing further heterocyclic rings · CPC title

• A61K31/519 Primary

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