A Phase 2/3 Study to Characterize and Evaluate the Efficacy, Safety, and Tolerability of hu14.18K322A Treatment Given in Combination With Chemotherapy in Participants With High-Risk Neuroblastoma
Neuroblastoma is the most common type of solid cancer found outside the brain in young children. Generally, it affects children younger than 5 years old, with the average age when it is found being just 2 years. Most patients have 'high-risk' disease, with spread of the disease to different sites (metastases). This multinational study aims to find out how effective and safe the treatment of a monoclonal anti-GD2 antibody hu14.18K322A (daretabart) is when used together with chemotherapy to treat children and young people who have high-risk neuroblastoma.
• 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.