B7-H3 CAR-T Infusions Via Dual Ommaya Reservoirs Show 14.6-mo Median OS in Recurrent Glioblastoma

B7-H3 is over-expressed in >70% of glioblastomas, and an intracranial B7-H3–directed autologous CAR-T product was tested in a first-in-human, dose-escalation Phase 1 study (NCT05474378). Nine heavily pre-treated patients (post-temozolomide relapse; median prior lines = 2) received monthly intratumoral ± intraventricular doses for up to six cycles. No grade 4/5 CRS or ICANS occurred; tumor-inflammation-associated neurotoxicity (TIAN) followed 81% of infusions but was reversible with anakinra + dexamethasone. With a median follow-up of 14.6 months, mOS reached 14.6 mo (95% CI 2.3–26.8), nearly doubling the historical post-progression survival of 8 to 9 months. Four patients remain alive ≥ 22 mo. CAR-T exposure in the cerebrospinal fluid correlated with B7-H3 expression.