EXTH-133. Activity of Berubicin, a novel anthracycline, in Pediatric Diffuse Midline Glioma (DMG) cells: Preliminary data and future possibilities

Berubicin is a unique anthracycline engineered to cross the blood-brain barrier (BBB). It has been tested in a global trial of adults with glioblastoma (GBM) vs. Lomustine with 252 patients randomized (2:1) for treatment after failure/recurrence of primary therapy for their disease. The trial showed that Berubicin was active in this disease with similar primary outcomes (Overall Survival [OS]) as Lomustine, showing that Berubicin does, indeed, have activity in GBM. Importantly, there was no evidence of cardiotoxicity based on intensive evaluations during the study (ECG, ECHO, troponin measurements) despite over 2 years of treatment. Therefore, the potential of Berubicin in pediatric diffuse midline glioma (DMG) is being explored in studies at University Children’s Hospital Zurich, which will include in vitro as well as in vivo studies. The preliminary results in patient-derived (PDX) DMG cell models show high activity (IC50 of 100-1000 nM), suggesting that there may be better efficacy than Lomustine (IC50 2-15 µM) and Temozolomide (>100 µM) against these same tumors. The study will be expanded to 8-10 different DMG models as well as in vivo testing incorporating combination therapy with ONC201 (dordaviprone), which is in clinical trials for DMG and under FDA review for approval expected later this year. Additional data from these studies will be presented and discussed.