A Multi-Arm, Multi-Stage Platform Trial For Relapsed Neuroblastoma

Despite advances with the introduction of anti-GD2 immunotherapy,there is a major unmet need to develop new drugs for treatment of high-risk neuroblastoma. Around half of patients relapse despite intensive therapies,and outcome following relapse is dismal (<10% long term survival). The BEACON2 trial will confirm which combination of drugs tested in the phase II BEACON study should be taken forward and identify novel combinations that further improve survival in this patient group. Based on our experience in a previous trial (BEACON),the BEACON2 platform will focus on relapse patients and will have two tiers (Tier 1,a first relapse randomisation and Tier 2,to facilitate smaller dose confirmation expansion cohorts of novel regimens) to be most efficient. The network of sites will facilitate rapid recruitment and widen access to novel drugs globally. Overall aims: - To improve survival for children with relapsed neuroblastoma by developing novel combinations that are ready for clinical implementation - To establish a platform trial to evaluate novel combinations in relapsed neuroblastoma,within a seamless phase 2-3 trial that can lead to regulatory approvals and impact clinical practice; allowing dose confirmation cohorts for novel combinations - To evaluate safety,activity,efficacy and quality of life for these novel combinations in relapsed neuroblastoma patients - To improve our understanding of relapsed neuroblastoma biology,tumour clonal evolution and develop biomarkers of response and resistance to direct the development targeted therapies by conducting a comprehensive biomarker sample collection.