This is a non-randomized, open label phase Ib/II dose-escalation and expansion study designed to define the recommended dose of anti-GD2-800CW in pediatric neuroblastoma patients. The aim of this imaging study is to determine a safe and effective dose of anti-GD2-800CW for intra-operative detection of neuroblastoma using NIR fluorescence.

Neuroblastoma is the most commonly diagnosed extracranial solid tumor in young children. It is a neural crest derived malignancy, which are the cells that give rise to the sympathetic nervous system, and can therefore be located in different body compartments. However, it occurs most frequently (80%) in the abdomen. Current treatment involves debulking surgery using standard-of-care, not assisted by intra-operative visualization of the tumor. In this current situation there is, i) a high risk of severe complications such as bleeding or unplanned nephrectomy (40%), ii) a high chance of >10% residual tumor tissue, and iii) difficulty distinguishing neuroblastoma subtypes with varying malignancy. Therefore, there is a high need for new tools enabling tumor-specific intra-operative visualization to assist the surgeon. This will reduce surgical complications and ensure neuroblastoma cells can be visualized and resected during surgery. Over the past years, Fluorescence Guided Surgery (FGS) has proven to be a useful intraoperative tool to increase the visibility of the tumor in various adult cancers. Our group has developed and validated a tumor-specific fluorescent agent, anti-GD2-800CW, that can be used to visualize neuroblastoma during surgery. Anti-GD2-800CW consists of two substances. Firstly, the monoclonal antibody anti-GD2, also known as Qarziba or Dinutuximab-beta, which binds to Disialoganglioside 2 (GD2), a tumor-associated antigen specifically expressed by neuroblastoma, most melanomas and several other tumors. Immunotherapy with anti-GD2 is now standard therapy for high-risk neuroblastoma treatment in patients aged 12 months and above. Secondly, the near-infrared (NIR) fluorescent dye, IRDye800CW, which is used extensively in clinical trials as fluorescent imaging agent without any known adverse events (AEs). The aim of this study is to investigate the safety and efficacy of this novel agent, anti-GD2-800CW, to visualize neuroblastoma during surgery.

Inclusion Criteria:

• Patients with the diagnosis of neuroblastoma as defined by histopathology (confirmed by the PMC Department of Pathology), who will be operated for NB as standard of care procedure
• Patients older than 1 year of age and not older than 18 years.
• Written informed consent from patients and/or from parents or legal guardians, according to local law and regulations

Exclusion Criteria:

• Previous treatment with Dinutuximab-beta, either alone or in combination with chemotherapy
• Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within during the screening period and before the administration of the IMP.
• Breast feeding.
• Sexually active participants not willing to use highly effective contraceptive method (pearl index <1) as defined in CTFG HMA 2020 (Appendix I) during trial participation and until 6 months after end of protocol therapy.
• Patients that received prior treatment with chimeric antibodies.

Only IPD used in the results publication.