TRLS-06. 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

This trial (NCT04771897) is currently enrolling at 3 US sites; as of January 2023, a total of 8 patients have been enrolled. Enrollment of cohort 1 (2.4 mg/kg and 54 Gy) and cohort 2 (3.2 mg/kg and 54 Gy) are completed. Enrollment in the expansion cohort is on-going. To date, no dose-limiting toxicity has been observed and the combination of BXQ-350 plus radiation has been well tolerated. BXQ-350 is a nanovesicle formulation of Saposin C that induces apoptosis of cancer cells and an anti-tumoral immune response by lowering Sphingosine-1-Phosphate and increasing ceramides concentrations. Saposin C is a human protein encoded by the Psap gene and is an allosteric activator of enzymes involved in sphingolipid/ceramide metabolism. 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. 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 (3.2 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 favorably influencing the tumor microenvironment. 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 concurrently with radiation therapy followed by adjuvant BXQ-350 until disease progression. Multiple secondary parameters are included to characterize BXQ-350’s pharmacokinetic parameters and efficacy profile and to investigate potential biomarkers.