Dinutuximab beta in combination with chemotherapy in patients with refractory or relapsed neuroblastoma: A national prospective study (2020/ABM/01/00055).

10037 Background: The ChIm-NB-PL phase IIa trial (EudraCT: 2021-003832-96) evaluated the safety and efficacy of dinutuximab beta (DB) combined with chemotherapy (Cht) in children with relapsed or refractory high-risk neuroblastoma (RR-HRNB), a population with limited therapeutic options and poor prognosis. Methods: Twenty-eight patients aged 1–18 years with RR-HRNB received DB combined with temozolomide/irinotecan (TemIri) or with N5/N6 chemotherapy of the German Pediatric Oncology and Hematology Group (GPOH) protocol. DB was administered as a 5-day continuous infusion (10 mg/m²/day) every 21 days, concurrently with TemIri or sequentially after GPOH. Treatment allocation and number of cycles were individualized based on prior therapy, disease dynamics, metastatic burden, and toxicity. Responses were assessed after 3 and 5–7 cycles. The primary endpoint was safety and best response (complete or partial response); secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results: Between 2021 and 2025, 28 patients were enrolled (25% female). Median follow-up was 28.4 months. Median age was 40.9 months at diagnosis and 51.0 months at study entry. Eleven patients had refractory disease (Group 1), while 17 had relapsed or progressive disease (Group 2; 12 early and 5 late relapses). MYCN amplification was present in 9 patients, and 12 had involvement of more than one metastatic compartment. In Group 1, best response rate (BRR) was 91.7%, end-of-treatment response rate 75.0%, and metastatic complete response 58.3%; 1-year PFS was 0.67 ± 0.13. In Group 2, BRR was 87.5% (CR 56.3%, PR 31.3%), with higher BRR in late versus early relapse (100% vs 80%); 1-year PFS was 0.81 ± 0.09. Overall, 71.4% of patients were alive at last follow-up; 1-year PFS and OS were 0.75 ± 0.08 and 0.82 ± 0.07, respectively. Grade ≥3 non-hematologic toxicities occurred 42 times with TemIri and 35 times with GPOH (CTCAE v4.0). Neurotoxicity, pain, capillary leak syndrome, and cytokine release syndrome were comparable between regimens and consistent with DB monotherapy. Conclusions: DB combined with TemIri or GPOH chemotherapy demonstrates high antitumor activity with acceptable and manageable toxicity in children with RR-HRNB. Response-adapted sequencing and individualized chemotherapy selection may improve disease control, including metastatic responses, in this high-risk population. Clinical trial information: 2021-003832-96.