Feasibility study of prolonged administration of naxitamab, irinotecan, and temozolomide for patients with relapsed or refractory neuroblastoma.

TPS10058 Background: Neuroblastoma is a malignant childhood tumor of the sympathetic nervous system. Cure rates are unsatisfactory for patients with high-risk disease (approximate 3-year EFS 50%) with current standard of care therapy. For patients who relapsed, anti-GD2 based chemoimmunotherapy has become standard, though it often requires in-hospital administration. Naxitamab, a humanized anti-GD2 monoclonal antibody (mAb), is FDA approved for patients with relapsed or refractory (R/R) high-risk neuroblastoma (HR-NB) with metastatic disease restricted to bone or bone marrow (BM), and who have stable disease or minor/partial response to previous therapies. With an infusion duration of 30-60 minutes, grade 3 pain and infusion-related reactions are common (72% and 68% of patients respectively) and necessitate extensive nursing and provider resources that may preclude administration at many centers. Slowing the rate of infusion of naxitamab and other anti-GD2 mAbs is generally associated with lower rates and severity of acute toxicity. We have therefore opened a phase I feasibility trial of prolonged administration of naxitamab in combination with irinotecan and temozolomide. Methods: This is a phase 1, single treatment arm, modified 3+3 prospective trial in patients with R/R or progressive HR-NB. The primary objective is to identify a recommended safe and feasible prolonged infusion duration of naxitamab in combination with irinotecan and temozolomide, with a goal of still allowing outpatient administration. Patients are enrolled at the starting total infusion duration of 4 hours, with an escalating infusion rate at pre-defined timepoints; the total infusion duration will be extended or shortened in cohorts of 3-6 patients based on safety and adverse events (AEs) observed in the first cycle. Individual patients will be eligible for duration escalation or de-escalation depending on AEs observed. An expansion cohort will be enrolled at the recommended infusion time. Key eligibility criteria include diagnosis of R/R or progressive HR-NB or ganglioneuroblastoma, age 1-30 years at enrollment, documentation of disease per revised International Neuroblastoma Response Criteria (INRC), adequate performance level, and adequate organ function including BM. Key exclusion criteria include prior receipt of naxitamab, untreated CNS metastatic disease, and discontinuation of prior GD2 immunotherapy due to unacceptable toxicity other than allergic reaction. Secondary endpoints include response rate per revised INRC and survival outcomes. Correlative and exploratory investigations embedded within the trial include PK profiling of prolonged naxitamab infusion durations and evaluation of circulating biomarkers including circulating tumor DNA, tumor cells, and GD2 in the study population during anti-GD2 therapy. Clinical trial information: NCT07027748 .