A phase 1 study to evaluate the safety and tolerability of BXQ-350, a novel sphingolipid metabolism modulator, in pediatric diffuse intrinsic pontine glioma and diffuse midline glioma.

e14044 Background: Diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG) are aggressive brain tumors in children that have a poor prognosis. BXQ-350 is a novel biologic that combines Saposin C (SapC) and dioleoylphosphatidylserine (DOPS). Saposin C is an allosteric activator of sphingolipid metabolism that lowers systemic Sphingosine-1-Phosphate (S1P) and increases Ceramide. Ceramides are proapoptotic and mitigate chemoresistance. Conversely, S1P promotes cancer cell proliferation, activates multiple oncogenic pathways, and stimulates immuno-suppressor cell populations promoting a pro-tumoral microenvironment. Preclinical studies have shown its effectiveness against tumors and safety, making it a suitable candidate for testing in pediatric DIPG and DMG patients. Methods: This two-part, open-label, multi-center Phase 1 study assesses BXQ-350 in children aged who have recently been diagnosed with DIPG or DMG. The first part focuses on dose-escalation to find the maximum tolerated dose (MTD) or the highest planned dose (3.2 mg/kg) when used alongside radiation therapy, followed by maintenance dosing. The second part looks at the pharmacokinetics (PK), pharmacodynamics (PD), and the levels of BXQ-350 within the tumors of patients with confirmed DIPG/DMG. Safety and tolerability will be evaluated through monitoring adverse events (AEs), laboratory results, and disease response according to RANO criteria. Results: BXQ-350 has shown safety and tolerability in both adult and pediatric Phase 1 studies, reaching the highest planned dose without any dose-limiting toxicity (DLT). The study aims to confirm safety, MTD, PK/PD profiles, and initial efficacy. Secondary endpoints include the objective response rate (ORR), overall survival (OS), and quality of life (QoL). Conclusions: BXQ-350 shows potential as a treatment for pediatric DIPG and DMG. By combining it with standard radiation therapy, this study aims to enhance survival rates in this vulnerable population. Future trials may further define its clinical application and optimize dosing strategies. Clinical trial information: NCT04771897 .