Patterns of improvement following initial response in patients treated with naxitamab for relapsed/refractory high-risk neuroblastoma.
Authors: Mora Jaume , Chan Godfrey C. , Morgenstern Daniel A. , Amoroso Loredana , Nysom Karsten , Faber Joerg , Wingerter Arthur , Bear Melissa , Rubio-San-Simón Alba , Tornøe Karen , Düring Maria , Kushner Brian H. 
Published: June 2024

10033 Background: Treatment of high-risk neuroblastoma (HRNB), the most common extracranial solid tumor in pediatric patients, is associated with suboptimal efficacy outcomes. While monitoring responses to naxitamab and other anti-GD2 monoclonal antibodies is essential, there is limited evidence on the timing and magnitude of improved responses following first assessment. Here, we report the patterns of improvement following the initial response to naxitamab therapy, based on the results of 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 refractory/relapsed HRNB with residual disease in bone and/or bone marrow (BM) only. “Refractory” and “relapsed” disease comprised those with an incomplete response (partial response [PR], minor response [MR], or stable disease [SD]) per International Neuroblastoma Response Criteria (INRC) to induction therapy or to treatment for actively progressing or relapsed disease, respectively. Patients with soft tissue or actively progressing disease were excluded. Naxitamab was infused at 3 mg/kg/dose IV on Days 1/3/5 with GM-CSF administered SC on Days -4 to 5 (monthly cycles [C]). The primary endpoint was overall response rate (ORR), comprising those with a complete response (CR) or PR per INRC. Response assessments occurred between C2 and C3 and at prespecified timepoints thereafter. Results: The ORR in Trial 201 was 50% (26/52). At first assessment, the ORR was 37% (n=19), with 14 patients achieving CR. An additional 6/26 patients (23%) achieved a CR or PR after C3, of whom 4 went from MR to CR, and 2 from SD to PR. (One patient whose disease was not evaluable at first assessment and who later had a PR was included in the ORR but excluded from this response improvement analysis.) In addition to the 6 patients who achieved a CR or PR after C3, 2 patients with PR at initial assessment later achieved a CR, and 1 patient with initial SD achieved MR, totaling 9 patients with improved post-C3 responses, or 17% of the overall efficacy population. Among those with baseline disease in bone, post-C3 responses in the bone compartment improved in 6/50 patients (12%). Of these 6 patients, 5 had initial SD in bone and achieved a post-C3 CR or PR. Post-C3 responses in the BM compartment improved in 6/23 patients (26%) with baseline BM disease, of whom 5 had initial SD in BM and achieved a post-C3 CR. Naxitamab safety (N=74) has been reported previously. Conclusions: A considerable proportion (23%) of patients achieved a CR or PR only after C3. Among these patients, most had initial SD within specific bone or BM compartments before achieving a post-C3 CR/PR. Taken together, the results support the rationale for continued treatment of patients not achieving CR/PR at first assessment. Clinical trial information: NCT03363373 .