Updated overall survival, safety, and neurologic function outcomes from a phase 1 trial of bivalent chimeric antigen receptor (CAR) T cell therapy in recurrent glioblastoma (GBM).

2013 Background: We previously reported the safety, bioactivity, and preliminary efficacy of bivalent CAR T cells targeting EGFR and IL13Rα2 in 18 patients with recurrent GBM (Bagley, et. al, Nat Med 2025). Given that median follow-up time was only 8.1 months at the time of the data cut-off for that publication, we now report updated overall survival (OS) and safety data with longer follow-up time, as well as neurologic function outcomes. Methods: Eighteen patients with recurrent EGFR-amplified GBM were enrolled using a 3+3 design (dose levels: 5.0 x 10 6 , 1.0 x 10 7 , and 2.5 x 10 7 cells). Patients received a single intracerebroventricular (ICV) dose of CART-EGFR-IL13Rα2 cells. OS was defined as the time from the date of initial study treatment to the date of death from any cause, or censored at the last date of contact if the patient was not known to have died at the date of analysis cut-off (January 16, 2026). To capture changes in neurologic function over the course of the trial, patients were assessed prospectively using the Neurologic Assessment in Neuro-Oncology (NANO) scale. NANO is an objective clinician-reported outcome of neurologic function scored on nine domains, with a higher score indicating worse neurologic function. NANO scores were assessed at baseline prior to CART (day 0), on days 1, 4, 7, 10, 14, 21, and at the 1-month and 2-month visits post-CART. Results: With median follow-up time of 18.5 months, median OS was 12.0 months (95% confidence interval, 7.4 – 23.2 months) with 3 patients surviving greater than 18 months. Other than one patient with prolonged grade 1 neurotoxicity as previously described, no prolonged, late-onset, or unexpected toxicities were observed within this longer follow-up time, including no evidence of on-target off-tumor toxicity or secondary cancers. On day 1 post infusion, an increase in NANO scores was observed (mean increase in NANO score from baseline of 1.9; p=0.09), which resolved to baseline by day 4. Patient NANO scores were unchanged from baseline at one month (mean change 0.41; p=0.998) and two months (mean change 0.54; p=0.992) post infusion. Those who underwent retreatment with a second dose of CAR-T cells at the time of tumor progression (n=7) did not experience an increase in NANO score on day 1 (mean change 0.33, p=0.99), despite having a significant increase on day 1 following the first infusion (mean change 2.9, p=0.008). Conclusions: With over 18 months of median follow-up time, ICV delivery of CART-EGFR- IL13Ra2 cells in patients with recurrent GBM has not demonstrated long-term or delayed toxicities and is associated with promising OS outcomes that warrant continued clinical development. Neurologic function worsens immediately following infusion but recovers to pre-treatment baseline by one month following CAR T cell infusion. Clinical trial information: NCT05168423 .