Inclusion criteria, exclusion criteria and study summary
Neuroblastoma is one of the commonest childhood malignancies and accounts for 15% of paediatric cancer deaths. Prognosis for children with metastatic disease remains poor. In recent years antibody based immunotherapies have shown considerable promise in this area. This is a phase 1 study to test the toxicity and tolerability of combining i) radiotherapy targeting neuroblastoma cells (131-I mIBG therapy) ii) antibody targeting the ganglioside molecule GD2 on neuroblastoma cells (Dinutuximab beta Apeiron) iii) Nivolumab, an antibody that binds to the immune molecule PD-1. This novel combination is based on pre-clinical work demonstrating that these agents may work together to kill neuroblastoma cells and generate long term immunity against the tumour. Both 131-I mIBG therapy and Dinutuximab beta have been widely used in neuroblastoma, with therapeutic activity as single agents. Nivolumab has undergone paediatric phase I testing, but has not been widely used in neuroblastoma. This study will be performed in patients with relapsed or refractory neuroblastoma, for whom there are no other curative options. The first cohort of patients will receive 131-I mIBG therapy followed by treatment with Nivolumab. If there is no unexpected toxicity, the next cohort of patients with received 131-I mIBG, Nivolumab and a reduced (50%) dose of Dinutuximab beta. If this is tolerated then a larger cohort of patients will receive all 3 agents at the full dose. Imaging of the tumour, as well as detailed monitoring of the immune response will be performed (by serial blood tests) to seek evidence of anti-tumour effects.