Naxitamab for High-Risk Neuroblastoma

Recruiting at 22 trial locations

Overseen By Joris Wilms

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Y-mAbs Therapeutics

Must not be taking: Chemotherapy, Immunotherapy

Disqualifiers: Major organ dysfunction, Life-threatening infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 101 weeks

122 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called naxitamab for individuals with high-risk neuroblastoma, a cancer often affecting children but also occurring in adults. The goal is to determine if naxitamab, combined with an immune-boosting drug (GM-CSF), can aid patients whose cancer has not responded well to previous treatments. Participants will receive the treatment for up to 101 weeks, with a five-year follow-up to monitor long-term effects. Suitable candidates have neuroblastoma that has not improved with other treatments, particularly in the bones or bone marrow, and should have a life expectancy of at least six more months. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic anti-cancer therapy, including chemotherapy or immunotherapy, at least 3 weeks before starting the trial treatment.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that naxitamab, when combined with GM-CSF, has some safety data for patients with high-risk neuroblastoma. In previous studies, about 80% of patients required a slower infusion rate due to reactions. Additionally, 80% experienced at least one reaction that temporarily halted the infusion.

Naxitamab already has FDA approval for treating certain neuroblastoma patients, indicating it has been studied and deemed safe for specific uses. However, like any treatment, side effects may occur. Participants should consult their healthcare providers to understand the risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for high-risk neuroblastoma, which often include chemotherapy and surgery, Naxitamab offers a targeted approach. Naxitamab is a monoclonal antibody designed to directly target and attack cancer cells, potentially leading to more precise tumor elimination with less damage to healthy tissue. Researchers are excited about Naxitamab because it combines with GM-CSF to potentially enhance the immune system's ability to fight the cancer, offering a promising new avenue that could improve response rates and outcomes for patients facing this challenging disease.

What evidence suggests that naxitamab might be an effective treatment for high-risk neuroblastoma?

Research has shown that naxitamab, combined with GM-CSF (a substance that boosts the immune system), is promising for treating high-risk neuroblastoma, particularly in patients unresponsive to chemotherapy. Studies have demonstrated that this combination effectively shrinks neuroblastoma tumors in the bones and bone marrow. More than one-third of patients experienced positive results, and over a quarter achieved a complete response, with no detectable cancer. These findings suggest that naxitamab can be a strong option for challenging neuroblastoma cases. The FDA has approved this treatment, further supporting its effectiveness for this condition. Participants in this trial will receive the GM-CSF and naxitamab combination as part of the investigational treatment. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for children and adults with high-risk neuroblastoma that hasn't fully responded to previous treatments or is considered refractory. Participants should have a life expectancy of at least 6 months and their disease must be present in the bone or bone marrow, but not outside these areas. They shouldn't have had cancer therapy within the last 3 weeks and must not have severe organ dysfunction or active serious infections.

Inclusion Criteria

My neuroblastoma is high-risk and hasn't fully responded to treatment.

Life expectancy ≥ 6 months

I have been diagnosed with neuroblastoma.

Exclusion Criteria

My neuroblastoma is detectable outside of my bones and bone marrow.

I do not have a severe infection that is putting my life at risk.

My major organs are functioning well, except possibly my hearing, blood, kidneys, or liver.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Naxitamab and GM-CSF treatment in cycles, repeated every 4 weeks initially, then every 8 weeks, for up to 101 weeks

101 weeks

Multiple visits per cycle, including days -4 to 5 for GM-CSF and days 1, 3, 5 for Naxitamab

End of Treatment

End of treatment visit occurs approximately 8 weeks after the last treatment cycle

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment for up to 5 years

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Naxitamab

Trial Overview The study tests naxitamab combined with GM-CSF in patients with high-risk neuroblastoma over a period of up to 101 weeks. Naxitamab is an antibody targeting GD2 on cancer cells, while GM-CSF helps boost the immune system's response against the tumor.

How Is the Trial Designed?

Group I: GM-CSF + Naxitamab Experimental Treatment 1 Intervention

Each investigational cycle is started with 5 days of GM-CSF administered at 250 µg/m2/day in advance of the start of Naxitamab administration. GM-CSF is thereafter administered at 500 µg/m2/day on days 1 to 5. As standard treatment, Naxitamab is administered at 3 mg/kg/day on days 1, 3, and 5 totalling 9 mg/kg per cycle. Treatment cycles are repeated every 4 weeks until CR or PR followed by 5 additional cycles every 4 weeks (±1 week). Subsequent cycles are repeated every 8 weeks (±2 weeks) through 101 weeks from first infusion at the discretion of the investigator. After end of treatment patients will enter a long-term follow up for up to 3 years after end of treatment visit.

Naxitamab is already approved in United States for the following indications:

Approved in United States as Danyelza for:

• High-risk neuroblastoma in bone or bone marrow demonstrating a partial response, minor response, or stable disease to prior therapy

Who Is Running the Clinical Trial?

Y-mAbs Therapeutics

Lead Sponsor

Trials

26

Recruited

1,600+

Published Research Related to This Trial

In a study of 33 infants with high-risk neuroblastoma, anti-GD2 monoclonal antibodies (3F8 and naxitamab) were administered safely during or immediately after chemotherapy, with manageable side effects and no severe long-term toxicities reported.

The treatment showed promising long-term outcomes, with 17 out of 21 patients receiving 3F8 in complete remission after a median of 13.4 years, and 10 out of 12 naxitamab patients remaining relapse-free after a median of 3.1 years, indicating that high-risk neuroblastoma in infants can be highly curable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy with anti-GD2 monoclonal antibody in infants with high-risk neuroblastoma. Kushner, BH., Modak, S., Kramer, K., et al.[2022]

Naxitamab, a monoclonal antibody for treating high-risk neuroblastoma, has a safety profile where over 50% of pediatric patients experienced manageable adverse events like pain, hypotension, and bronchospasm, with some severe cases requiring careful monitoring.

The study emphasizes the importance of premedication and supportive therapies to manage these adverse events effectively, allowing patients to continue treatment and maximize the benefits of naxitamab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient administration of naxitamab in combination with granulocyte-macrophage colony-stimulating factor in patients with refractory and/or relapsed high-risk neuroblastoma: Management of adverse events. Mora, J., Chan, GC., Morgenstern, DA., et al.[2023]

Naxitamab is a humanized monoclonal antibody specifically designed to target GD2-positive cancers, including neuroblastoma and osteosarcoma, and has received accelerated approval from the US FDA for treating high-risk neuroblastoma in pediatric and adult patients.

The approval allows naxitamab to be used in combination with granulocyte-macrophage colony-stimulating factor for patients who have shown a partial or minor response, or stable disease after previous treatments, highlighting its potential efficacy in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naxitamab: First Approval. Markham, A.[2021]

In a study of 73 high-risk neuroblastoma patients in complete remission, treatment with naxitamab and GM-CSF resulted in a three-year overall survival rate of 82.4% and an event-free survival rate of 58.4%.

The treatment was generally well-tolerated, with only 5% of patients experiencing severe grade 4 toxicities, and the majority (79.5%) completed the therapy, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naxitamab combined with granulocyte-macrophage colony-stimulating factor as consolidation for high-risk neuroblastoma patients in complete remission. Mora, J., Castañeda, A., Gorostegui, M., et al.[2022]

In a study of 34 patients with high-risk neuroblastoma who did not respond completely to initial therapy, the combination of naxitamab, irinotecan, temozolomide, and GM-CSF showed a complete response rate of 29% and a significant improvement in overall survival (OS) and event-free survival (EFS) when treatment was started early.

Patients receiving early treatment (cohort 1) had a 3-year OS of 84.8% and EFS of 54.4%, which were significantly better than those in the late treatment group (cohort 2), highlighting the importance of timing in administering this chemo-immunotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Salvage Chemo-Immunotherapy with Irinotecan, Temozolomide and Naxitamab Plus GM-CSF (HITS) for Patients with Primary Refractory High-Risk Neuroblastoma Provide the Best Chance for Long-Term Outcomes. Muñoz, JP., Larrosa, C., Chamorro, S., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40067131/

A phase II trial of Naxitamab plus stepped-up dosing of GM ... In an international trial, naxitamab+GM-CSF was effective against chemo-resistant high-risk neuroblastoma (HR-NB), leading to approval by the ...

2. nature.com nature.com/articles/s41467-025-56619-x

The anti-GD2 monoclonal antibody naxitamab plus GM ... Naxitamab demonstrated clinically meaningful efficacy with manageable safety in patients with residual neuroblastoma in bone/BM.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06013618?term=Naxitamab&rank=10

NCT06013618 | Clinical Analysis of Naxitamab (hu3F8) in ... This is an prospective study to evaluate the safety and efficacy of naxitamab monotherapy or combined with chemotherapy or combined with chemotherapy and ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/31/10/1877/762209/A-Phase-II-Trial-of-Naxitamab-plus-Stepped-up

A Phase II Trial of Naxitamab plus Stepped-up Dosing of GM ... In an international trial, naxitamab + GM-CSF was effective against chemoresistant high-risk neuroblastoma (HR-NB), leading to approval by the FDA. We now ...

5. danyelzahcp.com danyelzahcp.com/efficacy/study-results/

Efficacy: Study Results | DANYELZA® (naxitamab-gqgk) In the DANYELZA Studies 12-230 and 201 initial analysis, more than 1/3 of patients responded and more than 1/4 achieved a complete response.

6. danyelzahcp.com danyelzahcp.com/safety/

Safety - Danyelza Explore the DANYELZA® (naxitamab-gqgk) safety profile. Review ARs and lab abnormalities in the clinical trials, and when to permanently discontinue.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/761171lbl.pdf

DANYELZA (naxitamab-gqgk) Label - accessdata.fda.gov The safety of DANYELZA in combination with GM-CSF was evaluated in patients with refractory or relapsed high- risk neuroblastoma in bone or bone marrow who had ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03363373

Study Details | NCT03363373 | Naxitamab for High-Risk ... Naxitamab for High-Risk Neuroblastoma Patients With Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/​or Bone Marrow.

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)03577-8/fulltext

963MO Naxitamab for the treatment of refractory/relapsed ... 963MO Naxitamab for the treatment of refractory/relapsed high-risk neuroblastoma (HR NB): Updated efficacy and safety data from the international, multicenter ...

10. danyelzahcp.com danyelzahcp.com/

DANYELZA® (naxitamab-gqgk) Eighty percent of patients required reduction in infusion rate and 80% of patients had an infusion interrupted for at least one infusion-related reaction.