Naxitamab-related adverse events within and across treatment cycles in patients with relapsed/refractory (R/R) high-risk neuroblastoma.

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10032 Background: Anti-GD2 monoclonal antibodies, including naxitamab, for the treatment of high-risk neuroblastoma (HRNB) are associated with adverse events (AEs), though few studies have characterized their frequency and patterns of presentation. A practical understanding of AEs can help clinicians expect and manage those requiring intervention. In this post hoc analysis, we report the frequency and severity of naxitamab-related AEs across infusions and treatment cycles, based on data from a prespecified interim analysis of Trial 201. Methods: Trial 201 (phase 2, NCT03363373) is investigating naxitamab plus granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with R/R HRNB with residual disease in bone/bone marrow only. Patients with soft tissue or actively progressing disease were excluded. Naxitamab was infused at 3 mg/kg/dose IV on Days (D) 1/3/5 with GM-CSF administered SC on Days -4 to 5 (monthly cycles [C]). Patients (N=74) were evaluated for safety (CTCAE v4.0), with frequency defined as % of patients reporting >1 events. Frequency of AEs of Grade ≥3 were evaluated for C1-C5. Results: Most (81%) naxitamab-related AEs were Grade 1 or 2. Grade ≥3 AEs reported in ≥10% of patients were hypotension (60% of patients), pain (54%), urticaria (19%), bronchospasm (18%), and abdominal pain (16%). The frequency of related hypotension Grade ≥3 (Grade 4, n=3) decreased across cycles, from C1 (47%) to C5 (33%) and across infusions, from C1D1 (43%) to C1D3 (18%) and C1D5 (11%). Similar decreases were seen during C2 to C5. Among patients with Grade ≥3 hypotension, 73% had their first event C1D1, of whom 34% and 31% had their second event C1D3 or C2D1, respectively. The frequency of related pain Grade 3 AEs (all preferred terms with word “pain”) decreased from C1 (53%) to C2 (37%), generally stabilizing thereafter with frequencies consistent across infusions. Most (77%) had their first event C1D1, of whom 82% had a second event C1D3. The frequency of related bronchospasm Grade 3 (no Grade 4 AEs) was relatively stable around 7% from C1 to C3, decreasing to 4% and 2% in C4 and C5, respectively. Patients generally experienced these events on D1 infusions with few reported D3 or D5. No consistent pattern was seen for Grade 3 urticaria. None of the Grade ≥3 AEs of hypotension, urticaria, pain or bronchospasm resulted in treatment discontinuation. Conclusions: The frequency of naxitamab related Grade ≥3 AEs changed over the course of therapy. Hypotension was most frequent C1D1, decreasing across infusions and cycles. Pain frequency peaked C1 and decreased in subsequent cycles, remaining stable across infusions. Bronchospasm events, though relatively rare, generally occurred D1 and decreased across infusions. The results underline the importance of initial and ongoing monitoring within and across cycles to ensure appropriate and timely management. Clinical trial information: NCT03363373 .