RAPID: A pilot feasibility study of rapid dinutuximab infusion in patients with relapsed/refractory (RR) high-risk neuroblastoma (HRNBL).

10013 Background: Dinutuximab is a key component of therapy for HRNBL and is widely used in the RR setting. Standard administration requires inpatient infusions of ~10 hours daily. Emerging pediatric and adult data support shorter infusion durations. Evaluating rapid infusion of dinutuximab (RID) with chemotherapy may reduce pain, facilitate outpatient delivery, and decrease healthcare burden. Methods: This prospective, single-institution pilot study enrolled patients from 11/2022-12/2025 following IRB approval. Eligible patients included those ≥1 year old with RR-NBL, adequate organ function, and prior dinutuximab exposure. Patients received chemoimmunotherapy consisting of dinutuximab 17.5 mg/m²/day for 4 days (over 2-4 hours) combined with irinotecan/temozolomide (ITD) or cyclophosphamide/topotecan (CTD) for up to 6 cycles. Outpatient administration was permitted after cycle 1 if tolerated. The primary feasibility endpoint was successful dinutuximab administration over ≤5 hours with ≤1 patient experiencing unacceptable toxicity (UT) during cycle 1 in a 10-patient cohort. Secondary and exploratory endpoints included infusion duration, serial pain scores assessed during and post-infusion, opioid use in morphine milligram equivalents (MME), toxicity, feasibility of outpatient administration, pharmacokinetics (PK) and human anti-chimeric antibody (HACA). Changes in MME were compared using a one-sample t-test. Results: Eleven patients (median age 14 years, range: 3-24) received ITD (n=6) or CTD (n=5). All patients met the primary feasibility endpoint. Median infusion time was 2 hours (range 2-4) across all cycles. One patient (3 years old), enrolled in the early post-transplant period developed UT (grade 3 ventricular dysfunction). The protocol was amended to exclude patients within 6 months of transplant, require dinutuximab tolerance within 2 months, and extend cycle 1 infusion to 4 hours for patients <12 years of age; this patient was replaced per protocol. Across cycles 1-6, mean pain score was 0.4 (SD 0.46), and mean opioid usage was 0.04mg/kg MME (SD 0.07), reflecting a 78% reduction of opioid use in cycle 1 RID compared to the pre-enrollment standard-infusion cycle (p<0.001). Outpatient RID was administered in seven patients without hospital admission; 1 patient was admitted for chemotherapy-related toxicity, 3 patients remained inpatient (social reasons). RID showed expected PK levels; HACA was noted in 1 patient. Most common grade 3 toxicities (27%): increased ALT and hypokalemia; 1 patient (with UT) had grade 4 toxicity (dyspnea, hypocalcemia). Conclusions: RID was feasible and well tolerated, including in the outpatient setting. Pain control was achieved with standard premedication and significantly reduced opioid requirements compared with standard infusion. These data support planned multi-institutional evaluation of RID. Clinical trial information: NCT05421897 .