SCRI-CARB7H3(s); B7H3-specific chimeric antigen receptor (CAR) T cel

Autologous CD4+ and CD8+ T cells lentivirally transduced to express a B7H3 specific chimeric antigen receptor (CAR) and EGFRt given via indwelling central nervous system (CNS) catheter

Patients with supratentorial tumors will be assigned to Arm A, and will receive their treatment into the tumor cavity. Patients with either infratentorial or metastatic/leptomeningeal tumors will be assigned to Arm B, and will have their treatment delivered into the ventricular system. The first 3 patients enrolled onto the study must be at least 15 years of age and assigned to Arm A or Arm B.

This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with autologous CD4+ and CD8+ T cells lentivirally transduced to express a B7H3-specific chimeric antigen receptor (CAR) and EGFRt. CAR T cells are delivered via an indwelling catheter into the tumor resection cavity or 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 the tumor resection cavity or 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 targets B7H3-expressing tumor cells. Patients will be assigned to one of 3 treatment arms based on location or type of their tumor.

Live record on ClinicalTrials.gov →

• Age ≥ 1 and ≤ 26 years
• Diagnosis of refractory or recurrent CNS disease for which there is no standard therapy, or diagnosis of DIPG or DMG at any time point following completion of standard therapy
• Able to tolerate apheresis, or has apheresis product available for use in manufacturing
• CNS reservoir catheter, such as an Ommaya or Rickham catheter
• Life expectancy ≥ 8 weeks
• Lansky or Karnofsky score ≥ 60

Inclusion criteria as written on the registry, trimmed. The full list, with exclusions, is on the live record.