Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor (GMCSF) and Isotretinoin for Consolidation of Patients With High-Risk Neuroblastoma in First Remission.

Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor (GMCSF) and Isotretinoin for Consolidation of Patients With High-Risk Neuroblastoma in First Remission. An International, Open-Label,Uncontrolled, Single-Arm, Multicenter, Phase 2 Trial

This is a single-arm, uncontrolled, international, multi-center, clinical,phase 2 trial, in patients ≥ 12 months of age with high-risk neuroblastoma in first remission. 120 patients will be enrolled to receive naxitamab + GM-CSF in combination with isotretinoin.

Inclusion Criteria:

1. Documentet neuroblastoma at time of diagnosis defined as

   1. Histopathology of solid tumor biopsy, or
   2. Bone marrow aspirate or biopsy indicative of neuroblastoma plus high blood or urine catecholamine metabolite levels

2. Documented high-risk disease at time of initial diagnosis defined as

   1. MYNC-amplified at stage L2, M or MS (according to International Neuroblastoma Risk Group (INRG)) of any age or
   2. MYCN-nonamplified with stage M (according to INRG) and diagnosed at ≥ 18 months of age or

3. Patient must have completed frontline therapy, and achieved one of the following:

   1. verified complete response according to INRC (bone marrow positive minimal residual disease is allowed as assessed by RTqPCR at site) after completion of induction and consolidation with or without autologous stem cell transplantation
   2. Verified partial response according to INRC for primary site and soft tissue, bone, and bone marrow metastases at pre-autologous stem cell transplantation evaluation (i.e., myeloablative chemotherapy + autologous stem cell transplantation required as part of frontline regimen). Furthermore, bone marrow response must be with ≤ 5% tumor (of total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy and bone response must be with ≤ 3 areas of abnormal uptake on 123I-MIBG scintigraphy

4. Age ≥ 12 months at trial enrollment

Exclusion Criteria:

1. Verified progressive disease during induction or consolidation therapy
2. Any systemic anti-cancer therapy, including chemotherapy, within 3 weeks prior to enrollment
3. Autologous stem cell transplantation within 6 weeks prior to enrollment or ongoing toxicity caused by the autologous stem cell transplantation at the discretion of the Investigator
4. Therapeutic 131I-MIBG within 6 weeks prior to enrollment
5. Prior anti-GD2 therapy
6. Performance status of < 50% as per the Lansky scale (patients less than 16 years of age) or Karnofsky scale (patients aged 16 years or older)