This phase I trial evaluated IL-13Rx2-targeted CAR-T cells in 65 patients with recurrent high-grade glioma. Locoregional CAR-T cell administration was feasible and well-tolerated. Stable disease or better was achieved in 50% of patients. Median overall survival for recurrent glioblastoma patients was 7.7 months, improving to 10.2 months in arm 5 (dual ICT/ICV delivery and optimized manufacturing). CNS increases in inflammatory cytokines were associated with CAR-T cell administration. Pretreatment intratumoral CD3 T cell levels were positively associated with survival.

Christine E. Brown, Jonathan C. Hibbard, Darya Alizadeh, M. Suzette Blanchard, Heini M. Natri, Dongrui Wang, Julie R. Ostberg, Brenda Aguilar, Jamie R. Wagner, Jinny A. Paul, Renate Starr, Robyn A. Wong, Wuyang Chen, Noah Shulkin, Maryam Aftabizadeh, Aleksandr Filippov, Ammar Chaudhry, Julie A. Ressler, Julie Kilpatrick, Paige Myers-McNamara, Mike Chen, Leo D. Wang, Russell C. Rockne, Joseph Georges, Jana Portnow, Michael E. Barish, Massimo D’Apuzzo, Nicholas E. Banovich, Stephen J. Forman, Behnam Badie