A Phase II Study of Naxitamab Added to Induction Therapy for Subjects with Newly DiagnosedHigh-Risk Neuroblastoma
Objective
Primary Objective: To evaluate the VGPR(+) rate (VGPR + CR rate) to naxitamab with standard induction therapy for subjects with newly-diagnosed high-risk neuroblastoma according to the 1993 International Neuroblastoma Response Criteria (INRC) and compare to relevant historical controls.
Secondary Objectives: To assess objective response rate (ORR) to naxitamab with standard 5 cycle induction therapy for subjects with newly-diagnosed high-risk neuroblastoma according to the 1993 and 2017 International Neuroblastoma Response Criteria (INRC). To assess the objective response rate (ORR) to naxitamab after 2 cycles of induction therapy for subjects with newly-diagnosed high-risk neuroblastoma according to the 1993 and 2017 International Neuroblastoma Response Criteria (INRC). To evaluate event-free survival (EFS), and overall survival (OS) for subjects receiving the combination of standard Induction chemotherapy and naxitamab. To assess the response rate of naxitamab in combination with salvage chemotherapy in subjects who have a poor response (as defined as PR/MR/SD/NR) after 5 cycles of induction.
Safety Objectives: To evaluate the safety and tolerability of naxitamab with standard induction therapy for subjects with newly-diagnosed high-risk neuroblastoma.
Exploratory Objectives: To examine anti-drug antibodies (ADA) levels and response To examine Curie scores and response To study levels of circulating GD2, and tumor cell GD2 expression with response to therapy To examine levels of circulating tumor DNA (ctDNA) and response To study the pharmacokinetics of naxitamab when combined with chemotherapy To study the immune response and identify immune markers by determining KIR/KIR-L and Fc receptor genotyping; measuring markers of cytotoxicity (granulocyte and NK Cell mediated); measuring cytokine levels, immune cell profiles. To evaluate pain in terms of narcotic use To examine the effects of naxitamab on stem cell mobilization and collection To establish a Beat Childhood Cancer database of HRNB clinical, radiological, genomic (DNA, RNA, proteomic, epigenetic, ctDNA), and cell line and xenograft generation to study the relationship between tumor phenotype/genotype and response including the identification of genomic subtypes based on induction response and for the use for future research
