Dinutuximab Beta Added to Temozolomide-Based Chemotherapy for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON Immuno Phase II Trial

Juliet C. Gray; Rebekah Weston; Cormac Owens; Adela Canete; Marion Gambart; Bram De Wilde; Karsten Nysom; Natasha van Eijkelenburg; Ruth Ladenstein; Aurora Castellano; Nicolas U. Gerber; Lynley V. Marshall; Giuseppe Barone; Alba Rubio-San-Simon; Antony Ng; Sucheta Vaidya; Soledad Gallego; Guy Makin; G. A.Amos Burke; Anthony McCarthy; Dermot Murphy; C. Michel Zwaan; Ricardo López-Almaraz; Sarah Jannier; Estelle Thebaud; Nadege Corradini; Dan Yeomanson; Lisa Howell; Deborah A. Tweddle; Martin Elliott; Dave Hobin; Dominique Valteau-Couanet; Gudrun Schleiermacher; Pascal Chastagner; Anne Sophie Defachelles; Benedicte Brichard; Sally George; Louis Chesler; Jennifer Laidler; Charlotte Firth; Grace Holt; Veronica Moroz; Andrew D.J. Pearson; Simon Gates; Keith Wheatley; Pam Kearns; Lucas Moreno

doi:10.1200/JCO-25-01868

Dinutuximab Beta Added to Temozolomide-Based Chemotherapy for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON Immuno Phase II Trial

Juliet C. Gray^*
, Rebekah Weston
, Cormac Owens
, Adela Canete
, Marion Gambart
, Bram De Wilde
, Karsten Nysom
, Natasha van Eijkelenburg
, Ruth Ladenstein
, Aurora Castellano
, Nicolas U. Gerber
, Lynley V. Marshall
, Giuseppe Barone
, Alba Rubio-San-Simon
, Antony Ng
, Sucheta Vaidya
, Soledad Gallego
, Guy Makin
, G. A.Amos Burke
, Anthony McCarthy

Dermot Murphy, C. Michel Zwaan, Ricardo López-Almaraz, Sarah Jannier, Estelle Thebaud, Nadege Corradini, Dan Yeomanson, Lisa Howell, Deborah A. Tweddle, Martin Elliott, Dave Hobin, Dominique Valteau-Couanet, Gudrun Schleiermacher, Pascal Chastagner, Anne Sophie Defachelles, Benedicte Brichard, Sally George, Louis Chesler, Jennifer Laidler, Charlotte Firth, Grace Holt, Veronica Moroz, Andrew D.J. Pearson, Simon Gates, Keith Wheatley, Pam Kearns, Lucas Moreno

^*Corresponding author for this work

Pediatrics

University of Southampton
University of Birmingham
Children’s Health Ireland
Instituto de Investigación Sanitaria, Fundación Jiménez Díaz
CHU de Toulouse
Ghent University Hospital
Rigshospitalet
Princess Máxima Center for Pediatric Oncology
Medical University of Vienna
IRCCS Ospedale pediatrico Bambino Gesù - Roma
University of Zurich
Royal Marsden NHS Foundation Trust
Great Ormond Street Hospital for Children NHS Foundation Trust
Hospital Infantil Universitario Nino Jesus de Madrid
University Hospitals Bristol and Weston NHS Foundation Trust
Hospital Vall d'Hebron & ARADyAL research network
Manchester University NHS Foundation Trust
Belfast Health and Social Care Trust
Hospital de Cruces
Hôpital de Hautepierre
CHU de Nantes
Centre Léon Bérard
Sheffield Children's NHS Foundation Trust
Alder Hey Children's NHS Foundation Trust
Newcastle University
The General Infirmary at Leeds
Birmingham Women's and Children's NHS Foundation Trust
Institut Gustave Roussy
Institut Curie (Paris)
CHU de Nancy
Centre Oscar Lambret
Cliniques Universitaires Saint-Luc
NIHR Biomedical Research Centres (BRC)

Research output: Contribution to journal › Article › Academic › peer-review

11 Citations (Scopus)

11 Downloads (Pure)

Abstract

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.

Original language	English
Pages (from-to)	176-187
Number of pages	12
Journal	Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume	44
Issue number	3
DOIs	https://doi.org/10.1200/JCO-25-01868
Publication status	Published - 12 Dec 2025

Bibliographical note

Publisher Copyright:
© 2025 American Society of Clinical Oncology

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SDG 3 Good Health and Well-being

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Dinutuximab Beta Added to Temozolomide-Based Chemotherapy for Children With Relapsed and Refractory NeuroblastomaFinal published version, 490 KBLicence: CC BY

Cite this

Gray, J. C., Weston, R., Owens, C., Canete, A., Gambart, M., De Wilde, B., Nysom, K., van Eijkelenburg, N., Ladenstein, R., Castellano, A., Gerber, N. U., Marshall, L. V., Barone, G., Rubio-San-Simon, A., Ng, A., Vaidya, S., Gallego, S., Makin, G., Burke, G. A. A., ... Moreno, L. (2025). Dinutuximab Beta Added to Temozolomide-Based Chemotherapy for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON Immuno Phase II Trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 44(3), 176-187. https://doi.org/10.1200/JCO-25-01868

@article{32432623d3dd4ca28798c728dcadb809,

title = "Dinutuximab Beta Added to Temozolomide-Based Chemotherapy for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON Immuno Phase II Trial",

abstract = "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 = "Gray, \{Juliet C.\} and Rebekah Weston and Cormac Owens and Adela Canete and Marion Gambart and \{De Wilde\}, Bram and Karsten Nysom and \{van Eijkelenburg\}, Natasha and Ruth Ladenstein and Aurora Castellano and Gerber, \{Nicolas U.\} and Marshall, \{Lynley V.\} and Giuseppe Barone and Alba Rubio-San-Simon and Antony Ng and Sucheta Vaidya and Soledad Gallego and Guy Makin and Burke, \{G. A.Amos\} and Anthony McCarthy and Dermot Murphy and Zwaan, \{C. Michel\} and Ricardo L{\'o}pez-Almaraz and Sarah Jannier and Estelle Thebaud and Nadege Corradini and Dan Yeomanson and Lisa Howell and Tweddle, \{Deborah A.\} and Martin Elliott and Dave Hobin and Dominique Valteau-Couanet and Gudrun Schleiermacher and Pascal Chastagner and Defachelles, \{Anne Sophie\} and Benedicte Brichard and Sally George and Louis Chesler and Jennifer Laidler and Charlotte Firth and Grace Holt and Veronica Moroz and Pearson, \{Andrew D.J.\} and Simon Gates and Keith Wheatley and Pam Kearns and Lucas Moreno",

note = "Publisher Copyright: {\textcopyright} 2025 American Society of Clinical Oncology",

year = "2025",

month = dec,

day = "12",

doi = "10.1200/JCO-25-01868",

language = "English",

volume = "44",

pages = "176--187",

journal = "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",

issn = "0732-183X",

publisher = "Lippincott Williams \& Wilkins",

number = "3",

}

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, López-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 2025, 'Dinutuximab Beta Added to Temozolomide-Based Chemotherapy for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON Immuno Phase II Trial', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 44, no. 3, pp. 176-187. https://doi.org/10.1200/JCO-25-01868

Dinutuximab Beta Added to Temozolomide-Based Chemotherapy for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON Immuno Phase II Trial. / Gray, Juliet C.; Weston, Rebekah; Owens, Cormac et al.
In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 44, No. 3, 12.12.2025, p. 176-187.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Dinutuximab Beta Added to Temozolomide-Based Chemotherapy for Children With Relapsed and Refractory Neuroblastoma

T2 - Results of the ITCC-SIOPEN BEACON Immuno Phase II Trial

AU - Gray, Juliet C.

AU - Weston, Rebekah

AU - Owens, Cormac

AU - Canete, Adela

AU - Gambart, Marion

AU - De Wilde, Bram

AU - Nysom, Karsten

AU - van Eijkelenburg, Natasha

AU - Ladenstein, Ruth

AU - Castellano, Aurora

AU - Gerber, Nicolas U.

AU - Marshall, Lynley V.

AU - Barone, Giuseppe

AU - Rubio-San-Simon, Alba

AU - Ng, Antony

AU - Vaidya, Sucheta

AU - Gallego, Soledad

AU - Makin, Guy

AU - Burke, G. A.Amos

AU - McCarthy, Anthony

AU - Murphy, Dermot

AU - Zwaan, C. Michel

AU - López-Almaraz, Ricardo

AU - Jannier, Sarah

AU - Thebaud, Estelle

AU - Corradini, Nadege

AU - Yeomanson, Dan

AU - Howell, Lisa

AU - Tweddle, Deborah A.

AU - Elliott, Martin

AU - Hobin, Dave

AU - Valteau-Couanet, Dominique

AU - Schleiermacher, Gudrun

AU - Chastagner, Pascal

AU - Defachelles, Anne Sophie

AU - Brichard, Benedicte

AU - George, Sally

AU - Chesler, Louis

AU - Laidler, Jennifer

AU - Firth, Charlotte

AU - Holt, Grace

AU - Moroz, Veronica

AU - Pearson, Andrew D.J.

AU - Gates, Simon

AU - Wheatley, Keith

AU - Kearns, Pam

AU - Moreno, Lucas

PY - 2025/12/12

Y1 - 2025/12/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105027570818

U2 - 10.1200/JCO-25-01868

DO - 10.1200/JCO-25-01868

M3 - Article

C2 - 41385757

AN - SCOPUS:105027570818

SN - 0732-183X

VL - 44

SP - 176

EP - 187

JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology

JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology

IS - 3

ER -

Gray JC, Weston R, Owens C, Canete A, Gambart M, De Wilde B et al. Dinutuximab Beta Added to Temozolomide-Based Chemotherapy for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON Immuno Phase II Trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2025 Dec 12;44(3):176-187. doi: 10.1200/JCO-25-01868

Dinutuximab Beta Added to Temozolomide-Based Chemotherapy for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON Immuno Phase II Trial

Abstract

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