Table 4 Clinical trials of epigenetically directed therapies in adult and pediatric high-grade gliomas from the past and ongoing. CNS – central nervous system; DIPG – diffuse intrinsic pontine gliomas; DLT – dose-limiting toxicity; GBM – glioblastoma; MTD – maximum tolerated dose; OS – overall survival; PFS – progression-free survival
Target | Intervention | Condition | Phase | Outcome of the primary endpoint | Response Biomarker |
|---|---|---|---|---|---|
HDAC family | Vorinostat | Progressive or recurrent GBM [75] | II | Well tolerated and modest improvement in PFS (NCT00238303) | Acetylated H2BK5, H3K9, and H4K8 |
| Â | Entinostat | Pediatric patients with solid tumors, including the CNS [78] | I | Tolerable safety profile and no DLTs (NCT02780804) | Global protein lysine acetylation |
Panobinostat MTX110 (Aqueous panobinostat) | DIPG [19] DIPG [76) | I I/II | The MTD is 10mg/m2/dose for progressive DIPG and 22mg/m2/dose for pre-progressive DIPG when given 3x/week for 3 weeks on/1 week off. DLTs include thrombocytopenia and neutropenia (NCT02717455) Tolerable safely profile and OS of 26.1 months (NCT03566199) | Not included | |
BET family | Birabresib | Recurrent GBM | II | Study terminated due to a lack of clinical activity (NCT02296476) | Not included |
PRMT5 | PRT811 | Advanced solid tumors, including high-grade gliomas | I | Toxicity profile and DLT, no results yet (NCT04089449) | No results yet |
EZH2 | Tazemetostat | Pediatric patients with relapsed/refractory solid tumors with EZH2 alteration | II | Objective response rate, no results yet (NCT03155620; NCT03213665) | No results yet |