For patients ≥547 days old, any age cut-off ≤40 months discriminated younger (superior EFS/OS) versus older patients; no cut-off was optimal. OCAYA diagnosed 2010-2022 (post-immunotherapy era) had superior outcomes versus 2003-2009. Stratification by comprehensive molecular biomarkers will likely best inform novel therapeutic strategies for OCAYA.

P1/2, N=160, Recruiting, University of Birmingham

In a metastatic neuroblastoma model, IL-18-expressing GD2.CAR-NKTs controlled tumors more effectively than IL-15-only cells, but mice in the IL-15/IL-18 group developed severe toxicities not observed in the IL-18-only group...Finally, targeted metabolomics showed that IL-18 drives broad metabolic reprogramming in CAR-NKTs including increased oxidative phosphorylation, glycolysis, glutaminolysis, and purine metabolism. These findings support the use of IL-18 in developing the next generation of cytokine-armed CAR-NKT cancer immunotherapies.

EFS/OS rates at 24 months were 88%/95% and at 36 months were 80%/95%. Naxitamab + nGM-CSF is a good option to consolidate first CR of HR-NB patients, including those who did not undergo MAT.

P1/2, N=186, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=27, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

In this single-center retrospective study, children with a median age 5.1 years (range, 2.0-11.1 years) with R/R HR-NB who were treated with >5 cycles of dinutuximab beta (10 mg/m2/day for 10-days per 35-day cycle), granulocyte-macrophage colony-stimulating factor (GM-CSF) and isotretinoin, plus chemotherapy, were included. No immune-related deaths occurred. Overall, cycles beyond the standard 5 cycles of dinutuximab beta with chemoimmunotherapy were effective and tolerable in pediatric patients with R/R HR-NB, demonstrating improved response and survival outcomes.

P=N/A, N=7, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2025 --> Nov 2026

P2, N=118, Not yet recruiting, New Approaches to Neuroblastoma Therapy Consortium

Naxitamb + GM-CSF is an attractive option for primary refractory osteomedullary disease, including in patients with a high disease burden.

Dinutuximab, approved for high-risk neuroblastoma, improved event-free survival when combined with cytokines with standard therapy alone (NCT00026312). Similarly, Naxitamab, in combination with GM-CSF, achieved an overall response rate in relapsed/refractory neuroblastoma (NCT03363373)...Additionally, Racotumomab (anti-NeuGcGM3) demonstrated a survival benefit in advanced non-small cell lung cancer, extending median overall survival compared to placebo (NCT01240447). Despite these advances, challenges remain in improving patient selection, reducing off-target toxicities such as neuropathic pain, and addressing resistance mechanisms. This review examines the latest developments in ganglioside-mediated cancer therapy, emphasizing current clinical outcomes, highlighting the need for more precise targeting approaches, and exploring rational combination strategies to enhance therapeutic efficacy.

P2, N=62, Recruiting, New Approaches to Neuroblastoma Therapy Consortium | Active, not recruiting --> Recruiting