891P Naxitamab treatment for relapsed or refractory high-risk neuroblastoma: Outcomes from the first prespecified analyses of the Pivotal 201 Trial

Abstract

Naxitamab is a humanized GD2-binding monoclonal antibody approved in the US with GM-CSF for the treatment of relapsed/refractory high-risk neuroblastoma (HR-NB) in the bone/bone marrow (BM). This accelerated approval was based in part on an ad hoc analysis of data from the registrational phase II 201 trial (NCT03363373). Here we report the first results of a prespecified analysis from this same trial. Trial 201 is an ongoing phase II trial evaluating naxitamab+GM-CSF in patients with relapsed/refractory HR-NB with residual disease limited to bone/BM. Patients with progressive or residual soft tissue disease were not eligible. Naxitamab was administered over 30-60 min in the outpatient setting on Days 1/3/5 with GM-CSF on Days –4 to 5; cycles were 28 days. Efficacy was evaluated by independent pathology and radiology review per revised International Neuroblastoma Response Criteria. Assuming an actual overall response rate (ORR; complete response [CR] + partial response [PR]) of 45%, a sample size of 37 patients was considered sufficient to ensure ≥90% power to exclude an overall response rate of ≤20% at an α-level of 0.05. At data cutoff (Dec 31, 2021) there were 52 patients in the efficacy population and 74 in safety. The ORR was 50.0% (26/52; 95% CI 36-64%) with a CR rate of 38.5% (95% CI 25-53%). The trial met the primary endpoint for the prespecified analysis as the lower 95% CI for ORR was >20%. Disease control rate (CR+PR+minor response+stable disease) was 78.8% (41/52; 95% CI 65-89%) The adverse event (AE) profile was like previous reports with most being infusion-related reactions including hypotension and pain. 44.6% (33/74) of patients experienced ≥1 treatment-emergent serious AE; 6.8% (5/74) patients discontinued naxitamab due to treatment-emergent AEs. There were no deaths related to naxitamab. Based on this prespecified analysis, naxitamab provides a significant and clinically relevant response in patients with relapsed/refractory HR-NB limited to bone/BM – frequent sites of residual disease. These efficacy results combined with a manageable safety profile demonstrate that naxitamab addresses a significant unmet medical need.