Naxitamab Enabled Transplant-Free Study in High-Risk Neuroblastoma (NEXT-NB)

Inclusion Criteria:

• Age

  1. Participants must be age ≤ 21 years at High-Risk NB diagnosis

  2. Participants must be >12 months of age at enrollment. Diagnosis

  3. Participants must have a pathologically confirmed diagnosis of neuroblastoma and classified as high risk by the criteria used by COG or SIOPEN at the time of diagnosis.

     Exception: patients who are initially diagnosed as non high-risk neuroblastoma, but later converted to high-risk neuroblastoma are also eligible.

     Prior Therapy

  4. Participants must have completed standard induction therapy for initial diagnosis of high-risk neuroblastoma (5-7 cycles of induction chemotherapy with or without anti-GD2 antibody as per section 4.2, may include an additional cycle of therapy given prior to starting HRNB induction), and local control (surgery). Participants will enroll after completion of upfront induction therapy.

     Disease Response

  5. Participants must have a disease response by revised 2017 International Neuroblastoma Response Criteria (INRC) at the end of standard 5-7 cycles of Induction of GEIR:

     o Overall INRC Response ≥PR or

     o Primary tumor ≥SD, AND soft tissue/metastatic bone ≥PR, AND bone marrow ≥MD*

     • Includes bone marrow response of minimal disease or complete response. Timing

  6. Start of therapy to occur ≤ 45 days after completion of last induction cycle (from last day of cycle).

     Organ Function Requirements

  7. Hematological: Hematological recovery as defined by ANC ≥750/μL (unsupported- >24 hrs off G-CSF and 7 days off pegylated filgrastim).

  8. Renal: Participants must have adequate renal function defined:

     o For participants < 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: [(0.413) X (Height in cm)] / SCr

     o For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: [(140-age) x (Wt in kg) x (0.85 if female)] / (72 x SCr)

  9. Cardiac: Adequate cardiac function defined as:

     • Shortening fraction of ≥28%, or
     • Ejection fraction of ≥50%

  10. Liver: Adequate liver function defined as:

      • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
      • ALT (SGPT) < 10 x upper limit of normal (ULN) for age

  11. Post-pubertal study participants must be willing to use a highly effective contraceptive method (i.e., achieves a failure rate of <1% per year when used consistently and correctly) from the time of informed consent (and assent, as applicable) until 6 months after study treatment discontinuation. Participants who are lactating must agree to stop breast-feeding.

  12. Informed Consent: All participants and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines and applicable local regulations.

Exclusion Criteria:

• 1. Participants who are less than 1 year of age 2. Participants that had progressive disease (PD) at any time post cycle 4 during upfront induction therapy.

  3. Participants who required additional therapy after the end of standard Induction (5-7 cycles) to achieve adequate response.

  4. Investigational Drugs: Participants who are currently receiving another investigational drug are excluded from participation.

  5. Anti-cancer Agents: Participants who are currently receiving other anticancer agents are not eligible. Participants must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.

  6. Infection: Participants who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.

  7. Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.