USE OF ERK5 INHIBITORS FOR TREATING GLIOMAS IN PEDIATRIC SUBJECTS
The present disclosure relates to uses of an ERK5 inhibitor, e.g., ERK5-in-1, for treating a glioma in a pediatric human subject. In certain embodiments, the glioma can be a pediatric high-grade glioma (PHGG), e.g., a diffuse intrinsic pontine glioma (DIPG), and/or a H3.3-mutated glioma (e.g., a H3K27M-mutated glioma). The present disclosure further provides pharmaceutical compositions and kits that include an ERK5 inhibitor.
1 . A method for treating a glioma in a pediatric human subject, comprising administering to the subject a therapeutically effective amount of an ERK5 inhibitor, wherein the ERK5 inhibitor is not (16E)-14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]-heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (TG02) or a pharmaceutically acceptable salt thereof.
2 . The method of claim 1 , wherein the glioma is selected from the group consisting of a pediatric high-grade glioma (PHGG), a diffuse intrinsic pontine glioma (DIPG), a H3-mutant glioma, a H3K27M-mutant glioma, a H3K27M-mutant DIPG, and a H3.3-mutant non-DIPG high grade glioma.
3 . The method of claim 1 , wherein the ERK5 inhibitor is an ERK5 specific inhibitor.
4 . The method of claim 3 , wherein the ERK5 specific inhibitor is ERK5-IN-1 or a pharmaceutically acceptable salt form thereof.
5 . The method of claim 1 , wherein the ERK5 inhibitor is a dual ERK5 inhibitor.
6 . The method of claim 5 , wherein the dual ERK5 inhibitor is BIX02189, XMD8-92, or a pharmaceutically acceptable salt form thereof.
7 . The method of claim 1 , wherein the ERK5 inhibitor is administered orally.
8 . The method of claim 1 , wherein the ERK5 inhibitor is administered in an amount between about 20 mg/m 2 and about 200 mg/m 2 per day.
9 . The method of claim 1 , wherein the ERK5 inhibitor is administered in an amount of about 35 mg/m 2 per day.
10 . The method of claim 1 , wherein the pediatric human subject has a body surface area of at least about 50 m 2 .
11 . The method of claim 1 , wherein (a) the pediatric human subject has a body surface area of at least about 55 m 2 , and the ERK5 inhibitor is administered in an amount of about 35 mg/m 2 per day or about 50 mg/m 2 per day, or (b) the pediatric human subject has a body surface area of at least about 50 m 2 , and the ERK5 inhibitor—is administered in an amount of about 65 mg/m 2 per day or about 85 mg/m 2 per day.
12 . The method of claim 1 , wherein the ERK5 inhibitor is administered cyclically.
13 . The method of claim 12 , wherein the number of cycles is from one to twenty-four cycles.
14 . The method of claim 12 , wherein the duration of each cycle is 28 days.
15 . The method of claim 1 , wherein the ERK5 inhibitor is administered intermittently.
16 . The method of claim 1 , wherein a second anti-cancer treatment is administered to the pediatric human subject.
17 . The method of claim 16 , wherein the second anti-cancer treatment is selected from the group consisting of a radiotherapeutic agent, a radiotherapy, temozolomide, and an EZH2 inhibitor.
18 . The method of claim 1 , wherein the glioma is a newly diagnosed glioma, a refractory glioma, a relapsed glioma, or a relapsed and refractory glioma.
19 . The method of claim 1 , comprising administering to the pediatric human subject a pharmaceutical composition, wherein the pharmaceutical composition comprises the ERK5 inhibitor, and a pharmaceutically acceptable carrier.
20 . A kit for treating a glioma in a pediatric human subject, comprising an ERK5 inhibitor, wherein the ERK5 inhibitor is not (16E)-14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]-heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (TG02) or a pharmaceutically acceptable salt thereof.