Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors.
Primary objectives
* To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).
Secondary objectives
* To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B). * To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).
Age ≤ 21 years of age
Primary CNS tumor
For Cohort A, must have evidence of relapsed or refractory non-brainstem CNS tumor
Adequate tumor tissue from primary tumor resection or biopsy for central pathology review (i.e., B7-H3 expression evaluation by immunohistochemistry [IHC] or H3K27M mutation if pontine lesion)
Age ≤ 21 years of age
Cohort A: relapsed/refractory non-brainstem CNS primary tumor AND tumor is B7-H3 positive
B7-H3 positive if non-pontine
OR H3K27-altered diffuse midline pontine glioma
Parallel
B7-H3-CAR T cells
DrugAutologous T cells transduced with a lentiviral vector expressing a B7-H3-CAR with a CD28z signaling domain and 41BB ligand (B7-H3-CAR T cells). Four (4) infusions of B7-H3-CAR T cells will be locoregionally administered via CNS reservoir catheter.
Maximum tolerated dose (MTD)
To determine the maximum tolerated dose for the locoregional delivery of autologous B7-H3-CAR T cells in patients with recurrent/refractory B7-H3- positive primary CNS tumors (Cohort A) or diffuse midline glioma (DMG) (Cohort B).
Radiographic response
To assess the efficacy, defined as sustained objective response, partial response (PR) or complete response (CR), observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).
Click on the lead sponsor to view all of their trials.
