What question did this study set out to answer?

The study aims to evaluate the safety and clinical activity of C7R-GD2 CAR T cell therapy in pediatric CNS tumors.

June 26, 2026Open Access

ID #768 Phase I study of intravenous and intracerebroventricular C7R-GD2.CAR T cell therapy for pediatric central nervous system (CNS) tumors

Key Points

The study aims to evaluate the safety and clinical activity of C7R-GD2 CAR T cell therapy in pediatric CNS tumors.
Phase I clinical trial conducted sequentially with cohorts receiving intravenous (IV) and intracerebroventricular (ICV) infusions of C7R-GD2 CAR T cells.
Participants included those with high-grade CNS tumors and alterations in H3K27, administered in varying doses with lymphodepleting chemotherapy.
Safety was monitored for dose-limiting toxicities (DLTs) and clinical/MRI stability assessments were conducted.
In the IV-only infusion group, there were no DLTs identified, with preliminary stability in 2 out of 3 patients on DL1.
In the concurrent ICV-IV infusion group, 2 DLTs were reported due to grade 3 tumor inflammation-associated neurotoxicity; 4 out of 6 showed clinical/MRI stability.
Low-grade neurotoxicity and cytokine release syndrome were observed; elevated pro-inflammatory cytokines were detected in CSF.

Abstract

Abstract H3K27-altered diffuse midline gliomas and recurrent high-grade CNS tumors have poor prognoses and limited treatments. GD2-CAR T cells armored with constitutively active IL7 receptor (C7R-GD2.CARTs) have shown therapeutic efficacy in select patients. We conducted a Phase I study with sequential cohorts to assess the safety and clinical activity of C7R-GD2.CAR T therapy with lymphodepleting chemotherapy. We first studied intravenous (IV)-only infusions (n = 3 at DL1 (10 million cells/m2) and n = 6 at DL2 (30 million cells/m²/2 doses)), with no DLTs. Then, we assessed concurrent intracerebroventricular (ICV)-IV C7R-GD2.CART infusions (n = 3, one ICV dose (5 × 106 cells) and two IV doses (15 million cells/m2)) given one week apart, with 2 DLTs secondary to gr 3 tumor inflammation-associated neurotoxicity (TIAN). We then administered sequential IV (10 million cells/m2) followed by ICV cycles given q4 weeks (n = 3 at ICV DL1 (2x106cells) and n = 2 at ICV DL2 (5 × 106 cells)), with no DLTs. In the sequential arm, on DL1, 2 patients demonstrated clinical/MRI stability after 11 and 5 cycles to date; 1 patient experienced progression after 4 cycles. On DL2, 1 patient exhibited clinical/MRI stability with 4 cycles to date; 1 patient experienced progression after 2 cycles. On the current sequential arm, treatment was well-tolerated with low-grade TIAN and cytokine release syndrome; there was clinical/MRI stability in 4/6 patients. Preliminary CSF analysis detected transient elevations in the pro-inflammatory cytokines TNF-a, IL-6, and IFN-g one week after treatment, correlating with patient fever and headache. CSF IFN-g and IL-1B/ IL-1F2 were detectable at low levels in select samples 4 weeks post-infusion. Single-cell CSF RNA sequencing showed increased activated antigen-presenting myeloid cells and cytotoxic innate-like lymphocytes following treatment. Correlative analysis is ongoing to better understand toxicity profiles and response to treatment and to optimize CAR T cell therapy for these patients.

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