Granted Patent B2

US 9,586,940 · App. 14/801,335 · Granted Mar 7, 2017

Abstract

Claims (11)

1. A method of treating breast cancer that is nonresponsive to treatment with trastuzumab, comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of Formula 1

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the compound, or a pharmaceutically acceptable salt thereof, is a stereoisomer selected from the group consisting of N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine and N-(3,4-dichloro-2-fluorophenyl)-7-({[(3 aR, 5 s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, or a pharmaceutically acceptable salt of the stereoisomer.

3. The method as in claim 1 or 2 , wherein the pharmaceutically acceptable salt is the salt of p-toluenesulfonic acid.

4. The method as in claim 1 , 2 or 3 , wherein the subject is human and the breast cancer has not been treated with trastuzumab.

5. The method as in claim 1 , 2 or 3 , wherein the subject is human and the breast cancer has been treated with trastuzumab.

6. The method as in claim 1 , 2 or 3 , comprising co-administering the compound of Formula 1 and trastuzumab.

7. The method as in claim 1 , 2 or 3 , wherein the subject is human and the breast cancer is PTEN-negative.

8. The method as in claim 1 , 2 or 3 , wherein the subject is human and the breast cancer is positive for mutations in the PIK3CA gene.

9. The method as in claim 1 , 2 or 3 , wherein the subject is human and the breast cancer expresses a truncated ErbB2 receptor that lacks the extracellular domain to which trastuzumab binds.

10. The method as in claim 1 , 2 or 3 , wherein the subject is human and the breast cancer overexpresses one or more RTKs selected from the group consisting of EGFR family members, IGF-1R and HGFR.

Assignments (6)