Multicenter phase 1 trial of intracranial delivery of B7-H3-targeting CAR-T cells for recurrent glioblastoma

Recurrent glioblastoma (rGBM) is a malignancy with few therapeutic options. A multicenter phase 1 trial in China evaluated intracranial delivery of autologous B7-H3-targeting CAR-T cell therapy (TX103) for rGBM. In this 3+3 dose-escalation trial, patients aged 18-75 years with B7-H3-positive (≥ 30%) rGBM received intracranial infusion of TX103 at three dose levels (2 x 10⁷, 6 x 10⁷, and 1.5 x 108 cells per infusion). Primary endpoints were safety, maximum tolerated dose (MTD), and recommend phase 2 dose (RP2D). Fifteen patients received a total of 72 intracranial infusions (13 underwent repeated infusions). TX103 was well tolerated, with no dose-limiting toxicities. MTD was not identified; 6 x 10⁷ cells per infusion was selected as RP2D. Treatment-related adverse events (TRAEs) included low-grade cytokine release syndrome (86.7%), sinus tachycardia (53.3%), vomiting (53.3%), hypertension (53.3%), and elevated intracranial pressure (46.7%). Three grade 3 TRAEs considered serious adverse events occurred (elevated intracranial pressure, epilepsy, and depressed consciousness); two at the highest dose level. From first infusion, the 12-month overall survival (OS) rate was 66.7%, and median OS was 10.1 months (95% CI 8.93-NR). Disease control was achieved in 8 of 14 evaluable patients. The authors conclude that intracranial TX103 infusion demonstrated acceptable safety and encouraging efficacy in rGBM.