CARv3-TEAM-E Dual-EGFR CAR-T Shows 0 DLTs and 6-Month Stable Disease in Recurrent GBM

CARv3-TEAM-E is a second-generation CAR-T construct that targets the mutant neoantigen EGFRvIII and secretes a T-cell–engaging antibody against wild-type EGFR, aiming to overcome glioblastoma’s antigen heterogeneity. In the INCIPIENT Phase 1 dose-escalation study (NCT05660369), seven adults with EGFRvIII-mutant and/or EGFR-amplified recurrent GBM, expected in about half of GBM patients, received lymphodepletion (fludarabine 30 mg/m² × 3 d + cyclophosphamide 500 mg/m² × 2 d) followed by up to six monthly intraventricular infusions of 10 × 10⁶ CAR-T cells via an Ommaya reservoir. Grade ≥3 treatment-related events were limited to transient neutropenia/febrile neutropenia (each n = 1). CRS was universal but mild (all grade 1–2, median duration 3 d); ICANS reached only grade 1 in a single patient. Five of seven patients achieved radiographic stable disease, including one patient with 6-month SD after a single infusion and another with 33% tumor shrinkage after two doses; the remaining two had early progression. All patients remain alive 3–8 months post-first infusion (historical median OS after first GBM recurrence is ~9 months on lomustine ± bevacizumab).