METHOD OF TREATING MEDULLOBLASTOMA WITH AN EZH2 INHIBITOR
The disclosure provides a method of treating a medulloblastoma in a subject in need thereof comprising administering to the subject a therapeutically-effective amount of an enhancer of a zeste homolog 2 (EZH2) inhibitor. In a preferred embodiment of this method, the subject is pediatric and the EZH2 inhibitor is Tazemetostat.
1 . A method of treating a medulloblastoma in a subject in need thereof comprising administering to the subject a therapeutically-effective amount of an enhancer of zeste homolog 2 (EZH2) inhibitor.
2 . The method of claim 1 , wherein the EZH2 inhibitor comprises
or a pharmaceutically-acceptable salt thereof.
3 .- 7 . (canceled)
8 . The method of claim 1 , wherein the EZH2 inhibitor is administered orally.
9 . (canceled)
10 . The method of claim 1 , wherein the EZH2 inhibitor is administered at a dose of between 10 mg/kg/day and 1600 mg/kg/day.
11 . The method of claim 10 , wherein the EZH2 inhibitor is administered at a dose of about 100, 200, 400, 800, or 1600 mg.
12 .- 13 . (canceled)
14 . The method of claim 1 , wherein the EZH2 inhibitor is formulated for administration to cerebral spinal fluid (CSF) by an intraspinal, an intracranial, an intrathecal or an intranasal route.
15 . (canceled)
16 . The method of claim 1 , wherein the EZH2 inhibitor is administered at a dose of between 230 mg/m 2 and 600 mg/m 2 twice per day (BID), inclusive of the endpoints.
17 . (canceled)
18 . The method of claim 1 , wherein the EZH2 inhibitor is administered at a dose of 240 mg/m 2 twice per day (BID), or at a dose of 300 mg/m 2 twice per day (BID).
19 . (canceled)
20 . The method of claim 1 , wherein the EZH2 inhibitor is administered at a dose of about 60% of the area under the curve (AUC) at steady state (ACUss) following administration of 1600 mg twice a day to an adult subject.
21 . (canceled)
22 . The method of claim 20 , wherein the EZH2 inhibitor is administered at a dose of at least 600 mg/m 2 per day.
23 . The method of claim 1 , wherein the EZH2 inhibitor is administered at a dose of about 80% of the area under the curve (AUC) at steady state (ACUss) following administration of 800 mg twice a day to an adult subject.
24 . (canceled)
25 . The method of claim 23 , wherein the EZH2 inhibitor is administered at a dose of at least 390 mg/m 2 twice per day (BID).
26 . The method of claim 1 , wherein the EZH2 inhibitor is administered at a dose of between 300 mg/m 2 and 600 mg/m 2 twice per day (BID).
27 . The method of claim 1 , wherein the EZH2 inhibitor is administered twice per day (BID).
28 . The method of claim 1 , wherein the subject is a pediatric subject.
29 . The method of claim 28 , wherein the subject is between 6 months and 21 years of age, inclusive of the endpoints.
30 . The method of claim 29 , wherein the subject is between 1 year and 18 years of age, inclusive of the endpoints.
31 . The method of claim 28 , wherein the subject is 10 years of age or less, or 5 years of age or less.
32 . (canceled)
33 . The method of claim 1 , wherein treating comprises preventing and/or inhibiting proliferation of a medulloblastoma cell.
34 . A method of treating medulloblastoma in a subject in need thereof comprising administering to the subject a therapeutically-effective amount of tazemetostat,
wherein the therapeutically effective amount is at least 300 mg/m 2 twice per day (BID), and
wherein the subject is between 6 months and 21 years of age, inclusive of the endpoints.