The combination of naxitamab with or without sintilimab (anti-PD-1) for the treatment of refractory/progressive neuroblastoma: A prospective, non-randomized, multicenter trial.

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e22014 Background: Although significant advancements have been made in the treatment of neuroblastoma (NB), many patients continue to develop refractory or progressive disease. Naxitamab, a humanized anti-GD2 monoclonal antibody, has been granted approval for the treatment of recurrent or refractory high-risk NB with bone or bone marrow lesions. Based on the results that GD2 antibody induces PD-1 upregulation in a preclinical model, leading to a synergistic anti-tumor effect when combined with an anti-PD-1 antibody, our aim was to assess the outcomes of NB patients with refractory or progressive disease treated with naxitamab combined with or without sintilimab (anti-PD-1) in China. Methods: This was an open-label, prospective, and multicenter trial for patients with refractory or progressive NB. Results: A total of 34 patients were enrolled between October 26, 2021, and January 3, 2025, with a median age of 3.8 years (range, 0.7-40.3 years). Among the patients, 5 (14.7%) were diagnosed with MYCN-amplified NB, while 27 (79.4%) presented with non-amplified MYCN. Prior to enrollment, 5 patients had received autologous stem cell transplantation, while 1 patient had undergone allogeneic stem cell transplantation. At the time of enrollment, 17 patients presented with progressive disease, while 17 had refractory disease. Treatment regimens included naxitamab+GM-CSF+sintilimab (n = 2), naxitamab+GM-CSF (n = 6), naxitamab+GM-CSF+chemotherapy (n = 12), and naxitamab+GM-CSF+chemotherapy+sintilimab (n = 14). No patients experienced grade 3-4 adverse events. One patient developed grade 2 hypothyroidism, and no sintilimab related adverse events were observed in the other patients. The median follow-up time was 14.8 months (range, 0.2–31.0). The efficacy of the treatment was evaluable in 25 patients, with the best responses being as follows: complete response (n = 12), partial response (n = 3), minor response (n = 2), stable disease (n = 6), and progressive disease (n = 2). The overall response rate (ORR) and disease control rate (DCR) were 85.0% and 92.0%, respectively. The DCR was 100% with sintilimab, versus 83.3% without. The 12-month progression-free survival (PFS) rates for patients with refractory and progressive disease were 79.4% and 35.6%, respectively (P = 0.014). The 12-month overall survival (OS) rates for patients with refractory and progressive disease were 92.3% and 59.3%, respectively (P = 0.054). For patients with refractory and progressive disease, those who received sintilimab therapy exhibited a higher 12-month PFS rate compared to those who did not undergo sintilimab treatment (76.9% vs. 44.2%, P = 0.059). Conclusions: Refractory or progressive NB is expected to benefit from the treatment regimen involving naxitamab in combination with sintilimab, though larger sample sizes are needed for validation. Clinical trial information: NCT06013618 .

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