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, 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.

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

All Authors

Gray, JC.

Weston, R.

Owens, C.

Canete, A.

Gambart, M.

De Wilde, B.

Nysom, K.

van Eijkelenburg, N.

Ladenstein, R.

Castellano, A.

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LTHT Author

Elliott, Martin

LTHT Department

Leeds Children's Hospital
Children & Teenage Oncology & Haematology

Publication Date

2025

Item Type

Journal Article

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.