Naxitamab With GM-CSF Efficacious in Chemo-Resistant High-Risk Neuroblastoma

In the phase 1/2 12-230 trial (NCT01757626), naxitamab (Danyelza) plus stepped-up granulocyte-macrophage colony-stimulating factor (GM-CSF) demonstrated strong antitumor activity and manageable toxicity in patients with primary refractory high-risk neuroblastoma in osteomedullary sites.¹

At the recommended phase 2 dose of 9 mg/kg per cycle, among 32 patients, 24 (75%) achieved complete response (CR). Of the 23 patients who had post-induction bone marrow metastases, 22 achieved CR. This high response rate persisted in patients with high disease burden, including those with Curie scores ranging from 10 to 25 (n = 14/20; 70%).

Furthermore, the 5-year progression-free survival and overall survival rates were 38% and 64%, suggesting the potential of a higher dosing regimen to achieve durable remissions and longer-term survival.

“The results support the role of immunotherapy in improving survival of patients with persistent disease post-induction[,] though the optimal immunotherapy regimen remains unknown,” wrote authors Kushner et al in the Journal of Hematology & Oncology manuscript.¹

In November 2020, the FDA granted accelerated approval to naxitamab, a GD2-targeted monoclonal antibody, for the treatment of adult and pediatric patients aged 1 year and older with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow after receiving priority review of its biologics license application.

The decision was backed by phase 1 findings from Study 12-230 as well as the phase 2 Study 201 trial (NCT03363373), only applying to those who had demonstrated a partial response, minor response, or stable disease to prior therapy (ie, no progressive disease after prior therapy). Unlike the population targeted by the FDA approval, which excludes those with progressive disease, the present analysis includes all chemotherapy-resistant patients from Study 12-230, except for those with disease in soft tissue and those with no progressive disease.

Along with this year’s addition of naxitamab to the National Comprehensive Cancer Network’s (NCCN) Clinical Practice Guidelines in Oncology as a Category 2A treatment, these findings not only solidify naxitamab’s clinical use in high-risk neuroblastoma, but also show the value of expanding the target population to patients with chemotherapy-resistant disease pending further validation.

Safety Findings

The safety profile was manageable and expected with the established profiles of naxitamab and other anti-GD2 monoclonal antibodies, with common adverse effects including grade 1 to 3 pain, hypo/hypertension, urticaria, fever, and bronchospasm. Even with the stepped-up dosage of GM-CSF, there were no associated toxicities.

“Outpatient treatment and low immunogenicity are additional welcome features of this immunotherapy,” the authors added.

About the Phase 1/2 12-230 Trial

Initiated in 2012, the phase 1/2 dose-escalation and dose-expansion study sought to characterize the safety and evaluate the activity of naxitamab plus GM-CSF in 186 patients with high-risk neuroblastoma, measuring co-primary end points of response and survival outcomes.²

In the expansion stage, patients were categorized into 3 groups: patients with primary refractory disease in the bone marrow (group 1), patients in second or later CR (group 2), and patients with persistent disease despite salvage therapy for relapse (group 3). The findings from groups 2 and 3 were not reported in the present publication and will be reported separately in the future.

REFERENCES

1. Kushner BH, Modak S, Mauguen A, et al. Naxitamab plus stepped-up dosing of granulocyte–macrophage colony-stimulating factor for primary refractory high-risk neuroblastoma: results of a phase I/II trial. J Hematol Oncol. Published online November 26, 2025. doi:10.1186/s13045-025-01770-7

2. Combination therapy of antibody Hu3F8 with granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with relapsed/refractory high-risk neuroblastoma. ClinicalTrials.gov. Updated January 7, 2025. Accessed December 1, 2025. https://www.clinicaltrials.gov/study/NCT01757626