Naxitamab for High-Risk Neuroblastoma

Recruiting at 19 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

Trial Summary

What is the purpose of this trial?

Children and adults diagnosed with high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone and/or bone marrow will be treated for up to 101 weeks with naxitamab and granulocyte-macrophage colony stimulating factor (GM-CSF). Patients will be followed for up to five years after first dose. Naxitamab, also known as hu3F8 is a humanised monoclonal antibody targeting GD2

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.

What data supports the effectiveness of the drug Naxitamab for high-risk neuroblastoma?

Naxitamab, when used with other treatments like chemotherapy and granulocyte-macrophage colony-stimulating factor, has shown promising results in treating high-risk neuroblastoma, especially when given early. In one study, 47% of patients treated early achieved complete remission, and the overall survival rate was significantly improved. ^{1 2 3 4 5}

Is naxitamab safe for humans?

Naxitamab has been studied in various clinical trials and is generally considered safe for humans, though it can cause side effects like pain, high blood pressure, and allergic reactions. Most side effects are manageable, and serious long-term issues are rare. ^{1 2 3 4 5}

How is the drug naxitamab unique for treating high-risk neuroblastoma?

Naxitamab is unique because it is a humanized monoclonal antibody that specifically targets GD2, a molecule found on neuroblastoma cells, and is used in combination with granulocyte-macrophage colony-stimulating factor to enhance the immune response. It is approved for outpatient administration, which can be more convenient for patients, and is effective even in cases where the disease has relapsed or is resistant to other treatments. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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 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]

References

1. United States 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Naxitamab combined with granulocyte-macrophage colony-stimulating factor as consolidation for high-risk neuroblastoma patients in complete remission. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Immunotherapy with anti-GD2 monoclonal antibody in infants with high-risk neuroblastoma. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Naxitamab: First Approval. [2021]

5. Switzerland 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. [2023]