A basket trial of autologous Anti-GD2 chimeric antigen receptor (CAR) T Cells in patients with relapsed or refractory GD2-positive solid tumors (TARGETS): study protocol for a phase I/IIa multicenter open-label trial

Chimeric antigen receptor T cell therapy has demonstrated remarkable success in hematologic malignancies, prompting growing interest in extending its application to solid tumors. Neuroblastoma, glioma, and osteosarcoma are representative GD2-positive solid tumors characterized by aggressive biology, high relapse rates following standard therapy, and poor clinical outcomes, particularly in the relapsed or refractory setting where effective treatment options remain limited. This clinical trial evaluates a novel autologous anti-GD2-CAR T cell therapy incorporating a newly engineered second-generation CAR construct targeting GD2, a clinically validated tumor-associated antigen. TARGETS is a prospective, phase I/IIa, first-in-human clinical evaluation of this investigational anti-GD2 CAR T cell product, open-label, single-arm, multicenter basket trial enrolling approximately 20 patients. The primary objectives are to determine the maximum tolerated dose and to assess safety, while secondary objectives include evaluation of preliminary anti-tumor activity. Following leukapheresis and Good Manufacturing Practice-compliant manufacturing of anti-GD2-CAR T cells, participants receive intravenous infusion after lymphodepleting chemotherapy. Dose escalation follows a conventional 3 + 3 design across three planned dose levels followed by phase IIa expansion for further evaluation of preliminary anti-tumor activity, with intensive inpatient monitoring after infusion and long-term follow-up extending up to four years. This study is expected to generate foundational safety and preliminary anti-tumor activity data to inform the further clinical development of GD2-targeted CAR T cell therapy for solid tumors. Thai Clinical Trials Registry, TCTR20251222009. Registered 22 December 2025.