ID #993 Intravenous GD2 CAR T-Cell Therapy in Pediatric and Young Adult Central Nervous System Tumors: Preliminary Data

Abstract Background Immunotherapy with chimeric antigen receptor (CAR) T cells targeting the disialoganglioside GD2 may represent a therapeutic option for pediatric patients with high-grade central nervous system (CNS) tumors. Here, we report preliminary findings from an ongoing academic phase I clinical trial (NCT05298995) conducted at the Bambino Gesù Children Hospital in Rome, Italy. Methods This phase-I multi-arm, dose-escalation/descalation trial enrolled patients aged 6 months-30 years with relapsed/refractory CNS tumors to evaluate the safety/feasibility of third-generation GD2 CAR-T cells expressing an inducible caspase-9 suicide gene (GD2-CART01) intravenously administered. Five dose levels and three treatment arms were planned: Arm A (embryonal tumors), Arm B (hemispheric high-grade gliomas), and Arm C (diffuse midline gliomas and rare CNS tumors). Results Twenty-two patients have been enrolled so far; five were screening failures and 17 received GD2-CART01. Cytokine release syndrome occurred in 97% of patients. Immune effector cell–associated neurotoxicity syndrome (ICANS) was observed in 29% of patients, exclusively in Arm A, while tumor inflammation–associated neurotoxicity (TIAN) occurred in 23% and was restricted to Arms B and C. Hematologic toxicity was observed in all patients. Steroids were required in 37% of patients and AP1903 in 21%. Two dose-limiting toxicities were reported. CAR T-cell expansion was detected in all patients in blood and cerebrospinal fluid, with persistence up to 18 months post-infusion in one patient with medulloblastoma. At week 6, the disease control rate was 42% (18% partial response, 24% stable disease). Median overall survival (OS) was 6.6 months (range, 1.2–24.5), with six-month and one-year OS rates of 47% and 32.3%, respectively. The most favorable outcomes were observed in one patient with diffuse intrinsic pontine glioma alive at one year post-infusion and in three patients with medulloblastoma treated at low disease burden. Conclusions GD2-CART01 is feasible in pediatric and young adult patients with high-risk CNS tumors, with encouraging preliminary efficacy.