ID #993 Intravenous GD2 CAR T-Cell Therapy in Pediatric and Young Adult Central Nervous System Tumors: Preliminary Data
Giada Del Baldo, Francesca Del Bufalo, Andrea Carai, Matteo Amicucci, Antonella Cacchione, Giovanna Stefania Colafati, Maria Vinci, Biagio De Angelis, Concetta Quintarelli, Angela Mastronuzzi, Franco LocatelliAbstract
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.