Unituxin (dinutuximab)

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

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

P2, N=41, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2025 --> Sep 2027

P2, N=42, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2025 --> Sep 2026

Immunotherapy further improved survival rates that included monoclonal antibody (Anti-GD2 MoAb/Dinutuximab) and cytokines (ie, IL-2 and GM-CSF, [33-37])...This allowed them to produce a CAR that targets a tumor-specific antigen. Following preparatory chemotherapy, the CAR T cell product is administered into the patient.

P1/2, N=47, Completed, Eli Lilly and Company | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Aug 2025

Profile C was found only in cell lines of the mesenchymal subtype. These findings support further investigation of GG composition and associated enzyme expression as potential biomarkers for risk stratification and treatment response in NBL.

P1, N=11, Recruiting, Children's Hospital Los Angeles | Suspended --> Recruiting | Phase classification: P4 --> P1 | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Jun 2025 --> Dec 2025

P1/2, N=47, Active, not recruiting, Eli Lilly and Company | N=117 --> 47 | Trial completion date: Apr 2025 --> Dec 2025

INV34-6 showed high avidity for GD2+/hB7-H3+ but not GD2+/hB7-H3- B78 cells, contrasting with the similar cell binding to these cells observed with the anti-GD2 antibody Dinutuximab (DINU). The bispecific antibodies, DINU, and a nontargeted bispecific control (bsAb CTRL) were conjugated with deferoxamine for radiolabeling with Zr-89 (t1/2 = 78.4 h)...Overall, bispecific antibodies binding GD2 and B7-H3 showed improved selectivity for targeting tumor cells expressing both antigens. This approach may enhance antitumor efficacy while addressing the toxicity limitations of current GD2-targeting therapies by reducing off-tumor GD2 binding in nerves.

Concurrent use of lorlatinib with anti-GD2 mAbs may be associated with severe pulmonary toxicities. Temporarily withholding lorlatinib during immunotherapy appeared to mitigate this risk.