METHODS FOR TREATING SYSTEMIC MASTOCYTOSIS AND GASTROINTESTINAL STROMAL TUMORS
The present disclosure provides improved methods of treating systemic mastocytosis and gastrointestinal stromal tumors in patients with hepatic impairment by administering a modified amount of avapritinib.
1 . A method of treating systemic mastocytosis or gastrointestinal stromal tumor (GIST) in a patient in need thereof, comprising:
i) assessing if the patient is hepatically impaired; and
ii) if the patient is identified as having severe hepatic impairment, administering a modified therapeutically effective amount of avapritinib or a pharmaceutically acceptable salt thereof in an amount equivalent to
a) 200 mg once daily to the patient in need of treating GIST;
b) 100 mg once daily to the patient in need of treating advanced systemic mastocytosis (AdvSM); or
c) 25 mg every other day to the patient in need of treating indolent systemic mastocytosis (ISM).
2 . The method of claim 1 , wherein if the patient is identified as not having severe hepatic impairment, administering a therapeutically effective amount of avapritinib or a pharmaceutically acceptable salt thereof in an amount equivalent to
d) 300 mg once daily to the patient in need of treating GIST;
e) 200 mg once daily to the patient in need of treating AdvSM; or
f) 25 mg once daily to the patient in need of treating ISM.
3 . The method of claim 1 , wherein the hepatic impairment is assessed by Child-Pugh scoring system.
4 . The method of claim 3 , wherein the Child-Pugh scoring system comprises assessment of encephalopathy grade, ascites, serum bilirubin concentration, serum albumin concentration, and prothrombin time.
5 . The method of claim 4 , wherein the patient has a severe hepatic impairment as assessed by a Child-Pugh Score of 10-15.
6 . The method of claim 1 , wherein the avapritinib is administered orally.
7 . The method of claim 1 for treating GIST, wherein the patient with severe hepatic impairment as assessed by a Child-Pugh Score of 10-15 is administered orally avapritinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 200 mg once daily.
8 . The method of claim 7 for treating GIST, wherein the GIST is characterized by a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation.
9 . The method of claim 8 , wherein the PDGFRA mutation is D842V.
10 . The method of claim 1 for treating AdvSM, wherein the patient with severe hepatic impairment as assessed by a Child-Pugh Score of 10-15 is administered orally avapritinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 100 mg once daily.
11 . The method of claim 10 , wherein the AdvSM includes patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).
12 . The method of claim 11 , where the patient has a platelet count of not less than 50×10 9 /L.
13 . The method of claim 1 for treating ISM, wherein the patient with severe hepatic impairment as assessed by a Child-Pugh Score of 10-15 is administered orally avapritinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 25 mg every other day.
14 . A method of treating systemic mastocytosis or gastrointestinal stromal tumor (GIST) in a patient, wherein the patient has severe hepatic impairment, comprising:
administering a modified therapeutically effective amount of avapritinib or a pharmaceutically acceptable salt thereof in an amount equivalent to
i) 200 mg once daily to the patient in need of treating GIST;
ii) 100 mg once daily to the patient in need of treating advanced systemic mastocytosis (AdvSM); or
iii) 25 mg every other day to the patient in need of treating indolent systemic mastocytosis (ISM).
15 . The method of claim 14 , wherein the hepatic impairment is assessed by a Child-Pugh scoring system.
16 . The method of claim 15 , wherein the Child-Pugh scoring system comprises assessment of encephalopathy grade, escites, serum bilirubin concentration, serum albumin concentration, and prothrombin time.
17 . The method of claim 16 , wherein the patient has a Child-Pugh Score of 10-15.
18 . The method of claim 14 , wherein the avapritinib is administered orally.
19 . The method of claim 14 for treating GIST, wherein the GIST is characterized by a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation.
20 . The method of claim 19 , wherein the PDGFRA mutation is D842V.
21 . The method of claim 19 , wherein patient is administered orally avapritinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 200 mg once daily.
22 . The method of claim 14 for treating AdvSM, wherein the patient is administered orally avapritinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 100 mg once daily.
23 . The method of claim 22 , wherein the patient has a platelet count of not less than 50×10 9 /L.
24 . The method of claim 14 for treating ISM, wherein the patient is administered orally avapritinib or a pharmaceutically acceptable salt thereof in an amount equivalent to 25 mg every other day.