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Lookup NU author(s): Professor Deborah TweddleORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
PURPOSE: Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HR-NBL) remain dismal. Here, we investigate addition of the anti-GD2 monoclonal antibody, dinutuximab beta (dB), to temozolomide (T)-based chemotherapy. MATERIALS AND METHODS: Patients with RR-HR-NBL were randomly assigned in a 1:2 ratio to receive chemotherapy alone or chemotherapy with dB, given concurrently as a 7-day infusion (10 mg/m2/24 h). The trial had a factorial design, with some patients also randomly assigned between chemotherapy regimens (T v T-topotecan [TTo]). Crossover to dB with To/cyclophosphamide was allowed for patients randomly assigned to chemotherapy alone with disease progression (PD). The primary outcome was best objective response (complete or partial) rate (overall response rate [ORR]) during six cycles of treatment. Progression-free (PFS), overall survival (OS), and safety were secondary outcomes. RESULTS: Sixty-five patients were randomly assigned to chemotherapy alone (3 T, 19 TTo) or with dB (6 dBT, 37 dBTTo). The median age was 4 years; 28 and 37 patients had refractory and relapsed diseases, respectively. Baseline characteristics were balanced between arms. The ORR was 30.2% (13 of 43) and 18.2% (4 of 22) in dB and non-dB arms, the median PFS was 11.1 months (95% CI, 4.3 to 15.5) for dB patients and 3.8 months (95% CI, 1.9 to 7.9) for non-dB patients, respectively. The median OS was 25.7 months (95% CI, 11.4 to not reached [NR]) for dB patients and 17.1 months (95% CI, 7.6 to 54.6) for non-dB patients (upper 95% CI, NR in dB arm). Thirteen of 22 patients in the non-dB arm crossed over to dB with cyclophosphamide/To because of PD. Neurotoxicity was more common in the dB arm (grade 1 and 2: 26% v 9%, grade 3: 2.3% v 4.5%), but other toxicities were similar. CONCLUSION: Within a randomized phase II setting, results observed with addition of dB to T-based chemotherapy in RR-HR-NB warrant further evaluation.
Author(s): Gray JC, Weston R, Owens C, Canete A, Gambart M, De Wilde B, Nysom K, van Eijkelenburg N, Ladenstein R, Castellano A, Gerber NU, Marshall LV, Barone G, Rubio-San-Simon A, Ng A, Vaidya S, Gallego S, Makin G, Burke GAA, McCarthy A, Murphy D, Zwaan CM, Lopez-Almaraz R, Jannier S, Thebaud E, Corradini N, Yeomanson D, Howell L, Tweddle DA, Elliott M, Hobin D, Valteau-Couanet D, Schleiermacher G, Chastagner P, Defachelles AS, Brichard B, George S, Chesler L, Laidler J, Firth C, Holt G, Moroz V, Pearson ADJ, Gates S, Wheatley K, Kearns P, Moreno L
Publication type: Article
Publication status: Published
Journal: Journal of Clinical Oncology
Year: 2026
Volume: 44
Issue: 3
Pages: 176-187
Print publication date: 20/01/2026
Online publication date: 12/12/2025
Acceptance date: 23/10/2025
Date deposited: 26/01/2026
ISSN (print): 0732-183X
ISSN (electronic): 1527-7755
Publisher: American Society of Clinical Oncology
URL: https://doi.org/10.1200/JCO-25-01868
DOI: 10.1200/JCO-25-01868
Data Access Statement: Data sharing statement available from: https://ascopubs.org/action/downloadSupplement?doi=10.1200%2FJCO-25-01868&file=DSS_JCO-25-01868.pdf
PubMed id: 41385757
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