CTIM-32. SAFETY AND TOLERABILITY OF INTRAVENTRICULAR INFUSION OF B7-H3.CAR-T CELLS IN RECURRENT GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma remains the most aggressive primary brain tumor. B7-H3 (CD276) represents a promising therapeutic target due to widespread expression in glioblastoma with minimal expression in normal brain tissue. We report the interim analysis of a first-in-human Phase 1 clinical study evaluating the safety and tolerability of intraventricular inoculation of B7-H3.CAR-T cells in patients with recurrent glioblastoma. METHODS We conducted a phase 1, dose-escalation study using a 3 + 3 design in patients with recurrent glioblastoma. Eligible participants received three weekly intraventricular infusions across six planned dose levels (2×10⁶ to 1×10⁸ CAR-T cells). Autologous CAR-T cells were manufactured using RNA electroporation. The primary endpoint was safety and tolerability; secondary endpoints included feasibility and preliminary efficacy. RESULTS Nine participants were enrolled across three dose levels: 2×10⁶ (n=3), 5×10⁶ (n=3), and 1×10⁷ (n=3) CAR-T cells per infusion. All patients completed the scheduled three weekly infusions. No dose-limiting toxicities occurred. Two patients experienced mild cytokine release syndrome; no patients developed moderate or severe CRS. No immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade was observed. No grade ≥3 adverse events were attributed to CAR-T cell infusion. Two patients experienced moderate headaches. No patients required ICU admission or treatment with anakinra or tocilizumab. The best radiographic response included partial response in 2 patients and stable disease in 2 patients, resulting in a disease control rate of 44%. One patient demonstrated a partial response at 24 weeks, which remained durable at 8 months post-infusion. The other patient had a partial response at the end of the DLT period.Median overall survival was 10.2 months from CAR-T cell infusion. CONCLUSION Intraventricular administration of B7-H3.CAR-T cells demonstrated an acceptable safety profile with no dose-limiting toxicities. Encouraging preliminary efficacy signals include a 44% disease control rate and median overall survival of 10.2 months, supporting continued dose escalation in this trial.