Abstract B055: Disease control in patients treated with naxitamab for refractory/relapsed high-risk neuroblastoma
Authors: Mora Jaume , Chan Godfrey C. , Morgenstern Daniel A. , Amoroso Loredana , Nysom Karsten , Faber Joerg , Wingerter Arthur , Bear Melissa , Rubio-San-Simon Alba , Tornøe Karen , Koep Sharif , Düring Maria , Kushner Brian H. 
Published: September 2024

Abstract
Background: High-risk neuroblastoma (HR-NB) is the most common extracranial solid tumor in children, frequently characterized by residual disease following induction therapy and by relapses. Traditional efficacy measures include complete response (CR) or partial response (PR), both associated with reductions in all disease compartments. Historically poor outcomes and variable treatment responses, particularly among patients with refractory and relapsed disease, underscore the need for insights into the disease control rate (DCR), a composite measure of nonprogression comprising overall response of CR, PR, minor response, and stable disease (SD). Naxitamab is an anti-GD2 humanized monoclonal antibody with established efficacy in patients with refractory/relapsed (R/R) HR-NB in bone and/or bone marrow (BM). In this post hoc analysis, we report the DCR with a 12-week minimum of SD calculated from start of naxitamab treatment, based on data from a prespecified interim analysis of Trial 201. Methods: Ongoing Trial 201 (phase 2, NCT03363373) evaluates naxitamab plus granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with R/R HR-NB with residual disease in bone/BM only. Patients with soft tissue or actively progressing disease were excluded. Naxitamab was infused at 3mg/kg/dose intravenously on Days 1/3/5 with GM-CSF administered subcutaneously on Days -4 to 5 (monthly cycles). Response was evaluated by independent central review using the 2017 International Neuroblastoma Response Criteria. Results: DCR in the overall efficacy population (N=52) was 63% (95% CI, 49%-76%). Patients with an incomplete response in bone and/or BM following induction therapy (refractory disease, n=26) or relapse therapy (relapsed disease, n=26) achieved DCR (95% CI) of 73% (52%-88%) and 54% (33%-73%), respectively. DCR (95% CI) for additional patient subgroups were as follows: with bone disease only at baseline (n=29), 59% (39%-76%); with both bone and BM disease at baseline (n=21), 71% (48%-89%); baseline Curie score (CS) of ≤2 (n=22), 68% (45%-86%); baseline CS ≥3 (n=30), 60% (41%-77%); with prior anti-GD2 therapy (n=13), 46% (19%-75%); and without prior anti-GD2 therapy (n=39), 69% (52%-83%). Conclusions: Patients with R/R HR-NB and residual disease in bone and/or BM treated with naxitamab+GM-CSF achieved a DCR of 63%, providing an important measure for patients at risk for disease progression. Disease control appeared consistent irrespective of baseline CS. While additional studies are needed, the observed trend toward better DCR in those without prior anti-GD2 therapy vs those with prior anti-GD2 therapy may partly reflect the predominance of patients with relapsed disease (12/13) in the latter subgroup.
Citation Format: Jaume Mora, Godfrey C. Chan, Daniel A. Morgenstern, Loredana Amoroso, Karsten Nysom, Joerg Faber, Arthur Wingerter, Melissa Bear, Alba Rubio-San-Simon, Karen Tornøe, Sharif Koep, Maria Düring, Brian H. Kushner. Disease control in patients treated with naxitamab for refractory/relapsed high-risk neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B055.