B7-H3–directed CAR T cell therapy was well-tolerated and demonstrated an acceptable safety profile in recurrent glioblastoma.
B7-H3–targeted CAR T-cell therapy (CAR B7H3) was found to have an acceptable safety profile through intraventricular (IVH) administration with no dose-limiting toxicities (DLTs) and no moderate or severe cytokine release syndrome (CRS) in patients with recurrent glioblastoma, according to data from a phase 1 study (NCT05366179) presented at the 2025 Society of Neuro-Oncology Annual Meeting.1
Results showed that patients who received CAR B7H3 through IVH administration (n = 9) at 2 x 106 (n = 3), 5 x 106 (n = 3), or 1 x 107 cells (n = 3) per infusion did not experience any instances of immune effector cell–associated neurotoxicity syndrome of any grade. Mild CRS occurred in 2 patients, and no CAR T-cell therapy–related adverse effects (AEs) of grade 3 or above were reported. Two patients experienced moderate headaches.
Regarding efficacy, best radiographic responses led to a 44% disease control rate (n = 4), comprising a 22% partial response rate (n = 2) and a 22% stable disease rate (n = 2).
“Glioblastoma remains the most aggressive primary brain tumor, with a median survival of 14.6 months and 5-year survival rates below 5%. B7-H3 is a promising therapeutic target due to its widespread expression in glioblastoma and minimal expression in normal brain tissue,” lead study author Yasmeen Rauf, MD, and colleagues wrote in a poster presentation of the data. Rauf is an assistant professor of neurology and neurosurgery in the Department of Neurology at the University of North Carolina in Chapel Hill.
This trial is the first evaluating the safety and tolerability of CAR B7H3 administered through IVH infusion in human patients to help determine the recommended phase 2 dose (RP2D) of the drug.1,2
The single-center, open-label, dose-escalation study is enrolling patients who are at least 18 years of age with histologically confirmed glioblastoma, a Karnofsky score greater than 60%, and measurable disease of at least 1 cm. Current or previous exposure to antiangiogenic agents is not permitted, and patients are required to have undergone at least 4005 cGy of radiation with concurrent temozolomide.2
Patients who are pregnant or lactating, have prior or concurrent malignancy whose natural history or treatment has the potential to interfere with efficacy or safety assessment, or active HIV or hepatitis B or C infection were not included in the study.
Patients in the trial are receiving up to 3 weekly IVH infusions of CAR B7H3 across six different doses: 2 x 106, 5 x 106, 1 x 107, 3 x 107, 6 x 107, and 1x108 cells per infusion.1 The escalation of dosages is determined by the DLTs experienced by patients for each dose.
The trial’s primary end points are number of patients with AEs, incidence of CRS, and incidence of neurotoxicity.2
Data reported from phase 1 of the trial indicates that primary safety objectives have been met, with CAR B7H3 being well tolerated in patients at doses up to 1x107 cells per infusion.
Secondary end points from the trial include identification of RP2D, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and duration of response (DOR).2
Among patients treated thus far, the median OS was reported 10.2 months from the time of first infusion of CAR B7H3. Data for other secondary endpoints like ORR, PFS, RP2D, and DOR has yet to be reported.
