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 - 2026/1/20
Y1 - 2026/1/20
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.
KW - Humans
KW - Neuroblastoma/drug therapy
KW - Temozolomide/administration & dosage
KW - Female
KW - Male
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Child
KW - Child, Preschool
KW - Antibodies, Monoclonal/administration & dosage
KW - Infant
KW - Adolescent
KW - Neoplasm Recurrence, Local/drug therapy
KW - Progression-Free Survival
UR - http://www.scopus.com/inward/record.url?scp=105027570818&partnerID=8YFLogxK
U2 - 10.1200/JCO-25-01868
DO - 10.1200/JCO-25-01868
M3 - Journal article
C2 - 41385757
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 -