Claims for Patent: 11,925,619

Summary for Patent: 11,925,619

Title:	Treatments with nirogacestat
Abstract:	The present disclosure relates to improved methods of treatment with nirogacestat.
Inventor(s):	Allison Lim, Shinta CHENG, Todd Webster SHEARER, Rex WILLIAMS, Kristin Patterson
Assignee:	SpringWorks Therapeutics Inc
Application Number:	US18/361,884
Patent Claims:	1. A method for therapeutic treatment of desmoid tumor in a patient in need thereof comprising administering to the patient an oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof, wherein the oral dosage provides upon initial oral administration to the patient a Cmax of less than 1000 ng/mL, wherein the method comprises orally administering to the patient 150 mg (free base equivalent dose) of nirogacestat or a pharmaceutically acceptable salt thereof twice daily, and the method further comprises upon the patient having an alanine transaminase (ALT) or aspartate aminotransferase (AST) of 3 to 5 times upper limit of normal (ULN), withholding the nirogacestat or pharmaceutically acceptable salt thereof until the ALT, AST, or both are resolved to no higher than 3 times ULN or baseline and then restarting oral administration of the nirogacestat or pharmaceutically acceptable salt thereof at a dose of 100 mg (free base equivalent dose) twice daily. 2. The method of claim 1, wherein the oral dosage is administered once daily. 3. The method of claim 1, wherein the oral dosage is administered twice daily. 4. The method of claim 1, wherein the desmoid tumor is progressive desmoid tumor. 5. The method of claim 1, wherein administration of the oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof provides a reduction in the risk of disease progression. 6. The method of claim 1, wherein administration of the oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof provides improvement of progression-free survival. 7. The method of claim 1, wherein administration of the oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof provides improvements in objective response rate and at least one quality of life assessment. 8. A method for therapeutic treatment of desmoid tumor in a patient in need thereof comprising administering to the patient an oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof, wherein the oral dosage provides upon initial oral administration to a human subject an AUCinf of less than 4000 ng·h/mL, wherein the method comprises orally administering to the patient 150 mg (free base equivalent dose) of nirogacestat or a pharmaceutically acceptable salt thereof twice daily, and the method further comprises upon the patient having an alanine transaminase (ALT) or aspartate aminotransferase (AST) of 3 to 5 times upper limit of normal (ULN), withholding the nirogacestat or pharmaceutically acceptable salt thereof until the ALT, AST, or both are resolved to no higher than 3 times ULN or baseline and then restarting oral administration of the nirogacestat or pharmaceutically acceptable salt thereof at a dose of 100 mg (free base equivalent dose) twice daily. 9. The method of claim 8, wherein the oral dosage is administered once daily. 10. The method of claim 8, wherein the oral dosage is administered twice daily. 11. The method of claim 8, wherein the desmoid tumor is progressive desmoid tumor. 12. The method of claim 8, wherein administration of the oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof provides a reduction in the risk of disease progression. 13. The method of claim 8, wherein administration of the oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof provides improvement of progression-free survival. 14. The method of claim 8, wherein administration of the oral dosage of nirogacestat or a pharmaceutically acceptable salt thereof provides improvements in objective response rate and at least one quality of life assessment. 15. The method of claim 1, wherein the method further comprises upon the patient having an ALT or AST of greater than 5 times ULN, permanently discontinuing treatment with the nirogacestat or pharmaceutically acceptable salt thereof. 16. The method of claim 8, wherein the method further comprises upon the patient having an ALT or AST of greater than 5 times ULN, permanently discontinuing treatment with the nirogacestat or pharmaceutically acceptable salt thereof.