Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Medicine. https://doi.org/10.1038/s41591-025-03874-6 Dr. Franco Locatelli et al.
Points
- GD2-targeting CAR T cells, GD2–CART01, showed encouraging efficacy in high-risk neuroblastoma patients.
- The trial reported a 66% overall response rate in the enrolled cohort, with 5-year overall survival at 42.67%.
- Grade 3 neurotoxicity was managed using an inducible caspase-9 suicide gene activated by rimiducid.
- Superior outcomes were observed in patients with low disease burden and earlier treatment initiation.
- GD2–CART01 cells persisted for at least 12 months in 64% of the treated patient population.
Summary
This phase 1/2 clinical trial evaluated the efficacy and safety of antidisialoganglioside (GD2)-targeting third-generation chimeric antigen receptor (CAR) T cells (GD2–CART01) in children with high-risk metastatic, relapsed, or refractory neuroblastoma. The final results encompass 35 enrolled patients and an additional 19 children treated under hospital exemption, totaling 54 patients. Primary endpoints included safety, maximum tolerated dose (MTD), overall response rate (ORR), and complete remission (CR) rates. Secondary endpoints assessed 5-year overall survival (OS) and GD2–CART01 persistence.
No new safety signals were identified. Grade 3 immune effector cell-associated neurotoxicity syndrome occurred in four children, successfully managed by rimiducid-activated inducible caspase-9 suicide gene. The MTD was established at 10 × 10^6 CAR+ cells per kg. For patients enrolled in the trial (n=32, excluding three with no evidence of disease), the ORR was 66% (21/32). CR rates at 6 weeks, 3 months, and 6 months were 37%, 34%, and 40%, respectively. GD2–CART01 persistence was observed for ≥12 months in 64% of trial patients.
With a median follow-up of 4.2 years, the 5-year OS for the trial cohort was 42.67%. In the target population (n=38, low disease burden at MTD, including eight consolidated in no evidence of disease), the ORR improved to 77%, with 5-year OS and event-free survivals of 68% and 53%, respectively. Superior outcomes were noted in patients treated after fewer lines of prior therapy and those whose lymphocyte collection occurred at diagnosis. These data confirm that GD2–CART01 induces durable remissions in this challenging patient population.
Link to the article: https://www.nature.com/articles/s41591-025-03874-6
References
Locatelli, F., Pagliara, D., De Ioris, M. A., Becilli, M., Del Baldo, G., Serra, A., Mastronuzzi, A., Cefalo, M. G., Li Pira, G., Leone, G., Bertaina, V., Fabozzi, F., Di Nardo, M., Rosignoli, C., D’Andrea, M. L., Crocoli, A., Vennarini, S., Sinibaldi, M., Di Cecca, S., … del Bufalo, F. (2025). GD2-targeting CAR T cells in high-risk neuroblastoma: A phase 1/2 trial. Nature Medicine, 1–11. https://doi.org/10.1038/s41591-025-03874-6
