TRLS-17. INTERIM CLINICAL, PHARMACOKINETIC, AND TECHNICAL REPORT OF A PHASE 2 STUDY OF SONODYNAMIC THERAPY (SDT) USING SONALA-001 TOGETHER WITH MR-GUIDED LOW-INTENSITY FOCUSED ULTRASOUND (MRGFUS) IN CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

Children with DIPG have limited treatment options and poor prognosis with median survival of 9-12 months. Preclinical studies reveal that sonodynamic therapy (SDT) via MR-guided focused ultrasound (MRgFUS) activates SONALA-001 (ALA) metabolite, protoporphyrin IX (PpIX), inducing tumor cell death and extending survival in glioma models.

We present preliminary data from an ongoing first-in-child drug-device trial (NCT05123534) of SONALA-001 SDT in children with DIPG aged ≥ 5 years post-radiation therapy. The trial evaluates the safety of ALA-SDT, preliminary efficacy and pharmacokinetics (PK) of SONALA-001 at 5mg/kg administered 6-12 hours before SDT and establishes the RP2D. Each cohort involves three subjects: the first receiving half-pons treatment 30-days apart; the others receiving entire pons treatment. Single-treatment approach was amended to allow up to 12 monthly-treatments.

Six patients (4M:2F, 5-12 years) in 2 cohorts received 22 SDT-treatments between August 2022 and February 2023. Sonication duration averaged 147 minutes. Five of 6 patients received repeated treatments. All were discharged post-procedure day 1 with no DLTs or related AE grade ≥ 3. For SONALA-001, the C_max occurred at end of infusion, followed by rapid clearance (15.7 mL/min/kg); plasma half-life of < 1 hour, indicating rapid distribution. The PpIX-C_max occurred 4-6 hours post-dose, declining with a longer mean half-life than SONALA-001 of 6 hours. Both C_max and AUC_all demonstrate circulating-PpIX and systemic exposure were significantly lower than for SONALA-001. Two of 6 patients achieved a partial response per RAPNO central-review, and 2 continue in the study treatment for 11 and 15 months, respectively.

SDT is an innovative and to-date well-tolerated strategy for children with DIPG post-initial radiotherapy. Sonications did not result in any adverse procedural effects. SONALA-001 exhibits rapid distribution and clearance, while PpIX PK align with metabolite formation. After dose escalation completion, dose-expansion at R2PD will offer insights into safety, PK, and efficacy.