Chidamide combined with dinutuximab beta, irinotecan and temozolomide for relapsed or refractory neuroblastoma in children: protocol for a prospective, single-centre, open-label, single-arm, phase II study in China

Introduction Relapsed or refractory neuroblastoma remains a major cause of treatment failure in paediatric oncology. Anti-disialoganglioside 2 (anti-GD2) antibody-based chemoimmunotherapy has improved response rates, but durable disease control remains uncommon. Preclinical data suggest that epigenetic regulation of GD2 synthesis and neuroblastoma cell state may contribute to anti-GD2 resistance. This protocol describes a phase II study of chidamide, a subtype-selective histone deacetylase inhibitor, combined with dinutuximab beta, irinotecan and temozolomide in children with relapsed or refractory neuroblastoma. Methods and analysis This is a prospective, open-label, single-arm, single-centre, exploratory phase II clinical study conducted at Tianjin Medical University Cancer Institute & Hospital, China. The study will recruit 27 participants aged 0–18 years with relapsed or refractory neuroblastoma who meet protocol-defined eligibility criteria. Each 21-day treatment cycle includes oral chidamide 5 mg/10 kg, maximum 30 mg per dose, twice weekly, starting on day 0 for the first two weeks, followed by one week off treatment; dinutuximab beta 10 mg/m2/day by continuous intravenous infusion on days 2–6, total 50 mg/m2; irinotecan 50 mg/m2/day intravenously on days 1–5; and temozolomide 100 mg/m2/day orally or intravenously on days 1–5. Participants will receive at least three cycles (unless discontinued earlier for protocol-defined reasons) and may continue for 3–10 cycles according to response and tolerability. The primary endpoint is objective response rate. Secondary endpoints include progression-free survival, event-free survival, duration of response, overall survival and safety. Exploratory endpoints include immune cell and cytokine profiling, tumour cell-state and biomarker analyses, GD2/ST8SIA1/YAP1 assessment and plasma circulating tumour DNA (ctDNA) ST8SIA1 methylation monitoring. Ethics and dissemination The study protocol V.3.0 dated 25 November 2025 was approved by the Medical Ethics Committee of Tianjin Cancer Hospital (approval number E20251314; approval date 3 December 2025). Written informed consent will be obtained before study-specific procedures. Results will be submitted for peer-reviewed publication and conference presentation. Trial registration number NCT07318831.