PEDIATRIC DOSING FOR TREATMENT OF CANCER WITH AN EZH2 INHIBITOR
The disclosure provides a method of treating a an INI1-deficient tumor 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 cancer in a pediatric subject in need thereof comprising administering to the subject a therapeutically-effective amount of an enhancer of a 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 8 , 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/kg/day.
12 . The method of claim 11 , wherein the EZH2 inhibitor is administered at a dose of about 800 mg/kg/day.
13 . (canceled)
14 . The method of claim 1 , wherein the EZH2 inhibitor is formulated for administration to cerebral spinal fluid (CSF).
15 . The method of claim 14 , wherein the EZH2 inhibitor is administered to cerebral spinal fluid by an intraspinal, an intracranial, an intrathecal or an intranasal route.
16 . The method of claim 8 , 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, or at a dose of between 230 mg/m 2 and 305 mg/m 2 twice per day (BID), inclusive of the endpoints.
17 . (canceled)
18 . The method of claim 8 , 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 8 , wherein the EZH2 inhibitor is administered at a dose corresponding to about 60% of the area under the curve (AUC) of a steady state plasma concentration (AUC SS ) following administration of 1600 mg twice a day to an adult subject.
21 . The method of claim 20 , wherein the EZH2 inhibitor is administered at a dose of about 600 mg/m 2 per day.
22 . (canceled)
23 . The method of claim 8 , wherein the EZH2 inhibitor is administered at a dose corresponding to about 80% of the area under the curve (AUC) of a steady state plasma concentration (AUC SS ) following administration of 800 mg twice a day to an adult subject.
24 . The method of claim 23 , wherein the EZH2 inhibitor is administered at a dose of about 390 mg/m 2 twice per day (BID).
25 . (canceled)
26 . The method of claim 8 , 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 . (canceled)
29 . The method of claim 1 , wherein the subject is between 6 months and 21 years of age, inclusive of the endpoints, or between 1 year and 18 years of age, inclusive of the endpoints.
30 . (canceled)
31 . The method of claim 1 , 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 cancer cell.
34 . A method of treating cancer 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.