DIPG-30. A Phase 1, Safety and Dose Escalation Study of BXQ-350 in Combination with Radiation in Pediatric Patients with Diffuse Midline Glioma or Diffuse Intrinsic Pontine Glioma

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2022-06, Vol.24 (Supplement_1), p.i25-i25
• Main Authors: O'Toole Dorris, Kathleen McCarthy, Fouladi, Maryam, Hummel, Trent, Takigiku, Ray, Tapolsky, Gilles, Curry III, Richard
• Format: Article
• Language: English
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noac079.087

The significance of sphingolipid metabolism in brain cancers has been demonstrated and enzymes involved in sphingolipid metabolism are being investigated as novel therapeutic targets for adult and pediatric brain cancers. Saposin C is a human protein encoded by the Psap gene and is an allosteric activator of enzymes involved in sphingolipid/ceramide metabolism. BXQ-350 is a nanovesicle of Saposin C that has broad anticancer activity, inducing apoptosis of cancer cells and an anti-tumoral immune response by lowering Sphingosine-1-Phosphate and increasing ceramides concentrations. Also, BXQ-350 is synergistic with radiation therapy. BXQ-350 was investigated in a Phase 1 dose-escalation safety study in pediatric brain cancer patients (NCT03967093); results showed that it was well-tolerated, a MTD was not established, and the safety profile warranted the investigation of combination studies at the highest dose tested (3.4 mg/kg). Additionally, results from a Phase 1 safety and dose escalation study in adult patients with advanced solid malignancies (NCT02859857) indicated that BXQ-350 was well tolerated and showed single agent activity with evidence of modulating sphingolipid metabolism and impacting the immune system positively. The primary objective of this dose-escalation study is to describe the safety profile and to determine the maximum tolerated dose of BXQ-350 in combination with radiation. BXQ-350 is administered intravenously in a modified Fibonacci cohort-based dose escalation design starting at 2.4mg/kg. Multiple secondary parameters are included to characterize BXQ-350’s pharmacokinetic parameters, efficacy profile and investigate potential biomarkers. This trial is currently enrolling at 3 US sites; as of January 2022, enrollment of cohort 1 (2.4 mg/kg and 54 Gy) has been completed while enrollment in cohort 2 (3.2 mg/kg and 54 Gy) is on-going. To this date, no dose-limiting toxicity has been observed and the combination BXQ-350 plus radiation has been well tolerated. Current results will be presented.