NCT05768880

Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors

Phase 1 Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 72 (estimated)
• Sponsor: Seattle Children's Hospital · Academic / Other
• Sex: All
• Age: 1 Year – 26 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with SC-CAR4BRAIN, an autologous CD4+ and CD8+ T cells lentivirally transduced to express to express combinations of B7-H3, EGFR806, HER2, and IL13-zetakine chimeric antigen receptors (CAR). CAR T cells are delivered via an indwelling catheter into the ventricular system in children and young adults with diffuse intrinsic pontine glioma (DIPG), diffuse midline glioma (DMG), and recurrent or refractory CNS tumors. A child or young adult meeting all eligibility criteria, including having a CNS catheter placed into their ventricular system, and meeting none of the exclusion criteria will have their T cells collected. The T cells will then be bioengineered into a second-generation CAR T cell that target B7H3, EGFR806, HER2, and IL13-zetakine on tumor cells. Patients will be assigned to 1 of 2 treatment Arms based on the type of their tumor: * Arm A is for patients with DIPG (meaning primary disease localized to the pons, metastatic disease is allowed) anytime after standard radiation OR after progression. * Arm B is for patients with non-pontine DMG (meaning DMG in other parts of the brain such as the thalamus or spine) anytime after standard radiation OR after progression. This Arm also includes other recurrent/refractory CNS tumors.

Conditions

• Diffuse Intrinsic Pontine Glioma
• Diffuse Midline Glioma
• Recurrent CNS Tumor, Adult
• Recurrent, CNS Tumor, Childhood
• Refractory Primary Malignant Central Nervous System Neoplasm

Interventions

Type	Name	Description
BIOLOGICAL	SC-CAR4BRAIN	Courses of weekly intraventricular CNS administered SC-CAR4BRAIN infusions for 3 weeks, then 1 week off

Timeline

• Start date: 2023-05-05
• Primary completion: 2028-01-15
• Completion: 2043-12-31
• First posted: 2023-03-15
• Last updated: 2025-11-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study