Treatments with nirogacestat
The present disclosure relates to improved methods of treatment with nirogacestat.
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 C max 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 AUC inf 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.