GD2-targeting CAR T cells in high-risk neuroblastoma: a phase 1/2 trial

Antidisialoganglioside (GD2), third-generation chimeric antigen receptor (CAR) T cells (GD2-CART01) have shown encouraging efficacy in children with high-risk metastatic, relapsed, or refractory neuroblastoma in the interim analysis of a phase 1/2 clinical trial. We now present the final results obtained in all 35 patients enrolled and in 19 additional children selected with the same criteria of the trial and treated in a hospital exemption setting. Primary endpoints for the trial were safety, maximum tolerated dose, overall response rate (ORR) and complete remission rate at various timepoints. Secondary endpoints included 5-year overall survival (OS) and persistence of GD2-CART01. No new safety signals were observed. Grade 3 immune effector cell-associated neurotoxicity syndrome was diagnosed in four children and rapidly controlled with the activation of the inducible caspase-9 suicide gene by rimiducid. The maximum tolerated dose was 10 × 10⁶CAR⁺ cells per kg. The ORR of the patients enrolled in the clinical trial was 66% (21/32-excluding the three patients treated in nonevidence of disease). The complete remission rate at 6 weeks, 3 months and 6 months reached 37%, 34% and 40%, respectively. GD2-CART01 persisted ≥12 months in 64% of the patients enrolled in the clinical trial. With a median follow-up of 4.2 years, the 5-year OS for the trial cohort was 42.67%. In total, 38 of 54 children were treated with low disease burden at 10 × 10⁶ GD2-CART01 cells per kg (defined as the target population), including eight patients consolidated in nonevidence of disease after the first line. The ORR in the target population was 77%, the 5-year OS and event-free survivals were 68% and 53%, respectively. Substantially superior 5-year OS and event-free survivals were observed in patients treated after one or two lines of therapy versus those treated after ≥3 lines of therapy. Better results were observed in patients whose lymphocyte collection was performed at the time of diagnosis. These results confirm that GD2-CART01 can induce durable remissions in children with high-risk metastatic, relapsed, or refractory neuroblastoma. ClinicalTrials.gov identifier: NCT03373097 .