A new phase 2 clinical trial has demonstrated significant efficacy for naxitamab in treating relapsed/refractory high-risk neuroblastoma, offering hope for patients with limited treatment options. The trial evaluated naxitamab, an anti-GD2 monoclonal antibody, administered with GM-CSF in patients whose disease was limited to bone and/or bone marrow.
The global, single-arm, open-label study enrolled 74 patients, with 52 evaluated for efficacy. The trial achieved its primary endpoint with an overall response rate (ORR) of 50% (95% CI: 36–64%; P < 0.0001). Notably, 38% of patients achieved complete response (CR), while 12% showed partial response (PR).
Disease Compartment Response
Patients showed particularly strong responses in specific disease compartments. The bone compartment response rate was 58%, with 40% achieving CR. Even more impressive was the bone marrow compartment response rate of 74%, with all responding patients achieving CR. These results are especially significant given that bone and bone marrow are common sites for chemoresistant neuroblastoma cells.
Treatment Duration and Survival
The median duration of efficacy follow-up was 6 months, with a median duration of long-term follow-up reaching 21 months. The one-year progression-free survival (PFS) was 35%, with median PFS of 30 weeks. Importantly, the one-year overall survival rate was 93%, though median overall survival was not yet reached at data cutoff.
Safety Profile and Administration
The safety analysis revealed manageable adverse events, though requiring careful monitoring. Key findings include:
- All patients experienced at least one treatment-emergent adverse event
- Most common severe adverse events were infusion-related reactions
- No fatal treatment-related adverse events or cases of transverse myelitis
- 92% of infusions were administered in outpatient settings
- Median infusion time was 37 minutes
Treatment-related adverse events included:
- Hypotension (Grade 3-4 in 47% of patients in Cycle 1)
- Pain (Grade 3 in 54% of patients)
- Bronchospasm (Grade 3 in 6.8% of patients in Cycle 1)
Prior Anti-GD2 Treatment Response
An important finding was that 31% of patients who had previously received another anti-GD2 monoclonal antibody showed response to naxitamab. This suggests potential utility even in patients who have undergone prior anti-GD2 therapy.
Clinical Implications
The trial results demonstrate naxitamab's effectiveness as a single-agent therapy (with GM-CSF) in treating bone/bone marrow disease in relapsed/refractory high-risk neuroblastoma. The manageable safety profile, coupled with predominantly outpatient administration, represents a significant advance in treatment options for this challenging patient population.
Future Directions
While these results are promising, several areas warrant further investigation:
- Long-term survival outcomes
- Efficacy in patients with soft tissue disease
- Combination strategies with other therapeutic agents
- Optimal treatment sequencing with other anti-GD2 antibodies
The findings support naxitamab's role in the treatment landscape for high-risk neuroblastoma, particularly for patients with bone and bone marrow disease. Continued follow-up and additional studies will help further define its optimal use in clinical practice.
