A Safety and Efficacy Study of hu14 in High-Risk Neuroblastoma Patients

Prior treatment

• Patients who have undergone a prior allogeneic stem cell transplant \< 6 months ago or have undergone a solid organ transplant.
• Patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study except to manage allergic reactions
• Patients on any other immunosuppressive medications
• Patients who have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to study enrollment.
• If female, are breastfeeding, pregnant, or planning to become pregnant, or, if sexually active and of child-bearing potential, are unwilling to use an effective birth control method until 6 months after the last dose of study medication
• Ongoing need for any medication known or suspected to interfere with study treatment.

Other illness

• Any active uncontrolled infection at the time of enrollment. Any known history of infection with human immunodeficiency virus (HIV), or active or chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Patients with disease of any major organ system that would compromise their ability to withstand chemoimmunotherapy.
• Patients who have been diagnosed with any malignancy other than neuroblastoma.
• Patients with symptoms of congestive heart failure.
• Patients with a history of Grade 4 allergic reactions to anti-GD2 antibodies or reactions that required permanent discontinuation of the anti-GD2 therapy.

Lab values

• Do not meet the following required washout periods prior to the administration of the first dose of hu14.18K322A:
  • 14 days from prior systemic myelosuppressive chemotherapy.
  • 7 days from prior systemic biologic antineoplastic agents (e.g. anti-cancer agents not known to be myelosuppressive - not associated with reduced platelet or ANC counts).
  • 14 days from systemic steroids.
  • ≥12 weeks from large field radiation therapy (i.e., total body irradiation, whole abdominal, total lung, ≥50% pelvis).
  • 6 weeks from prior craniospinal radiotherapy or Iodine-131-metaiodobenzylguanidine (131I-MIBG) therapy.
  • 2 weeks from radiotherapy to the primary tumor bed.
  • ≥7 days from small treatment field radiation.
  • 14 days or 5 half-lives (whichever is longer) from last administration of an IMP.
  • \>7 days prior to study enrollment for drugs that are strong inducers or inhibitors of Cytochrome P450 3A4 (CYP3A4).
  • ≥21 days and with recovery of all associated toxicities from receiving cellular therapy (e.g., modified T lymphocyte cells, Natural Killer (NK) cells, dendritic cells).

Other

• Any contraindications to any of the study treatments.
• Patients with \>Grade 2 diarrhea.
• Patients who are on hemodialysis.
• Patients participating in or planning to participate in another study that is either blinded or involves an IMP

• Are ≥18 months to \<18 years of age at time of informed consent or assent.
• Are initially diagnosed with histologically proven HRNB with metastatic disease.
• Have evaluable or measurable disease per International Neuroblastoma Response Criteria (INRC)
• Have a Lansky performance status of ≥50 (≤16 years ) or Karnofsky performance status ≥50% (for \>16 years).
• Have recovered from the toxic effects of prior chemotherapies
• Are at least 2 weeks beyond any major tumor surgery
• Meet the following organ function criteria, as measured within 1 week prior to Investigational Medicinal Product (IMP) dosing:
  • BM function: i. Platelets ≥50 × 109/L ii. Absolute neutrophil count (ANC) ≥0.50 × 109/L
  • Renal function: i. Age-adjusted serum creatinine ≤1.5 × upper limit of normal (ULN) for age. ii. Estimated glomerular filtration rate (eGFR) at least 60 mL/min using the Schwartz formula.
  • Liver function: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3 × ULN and total bilirubin ≤1.5 × ULN.
  • Cardiac function: i. Shortening fraction ≥27% or ejection fraction of ≥50% on echocardiogram. ii. Corrected QT Interval on electrocardiogram (ECG) using the Fridericia formula (QTcF) ≤ 480 msec.
  • Lung function: i. Pulse oximetry considered normal in room air. No evidence of dyspnea at rest.
  • Central nervous system (CNS) function: i. Participants with a history of CNS disease must have no clinical or radiological evidence of active CNS disease at the time of study enrollment.
• If a fertile and sexually active woman of child-bearing potential (WOCBP), have a negative serum pregnancy test at Screening and then either a negative serum or urine test prior to each cycle and agree to use an acceptable and highly effective contraception method during the study and for at least 6 months after the last day of study treatment .
• If a fertile and sexually active male, agree to use condoms during the study and for at least 6 months after the last dose of study treatment
• If applicable based on age, are willing and able to provide voluntary written informed assent for participation in the study (as per local Institutional Review Board \[IRB\]/Independent Ethics Committee \[IEC\] requirements and if applicable based on regional age of consent) and to comply with all protocol requirements.
• Their parent or legal guardian (if applicable based on regional age of consent) is willing and able to provide voluntary written informed consent for the participant's involvement in the study.