Naxitamab for High-Risk Neuroblastoma

Recruiting at 8 trial locations

Overseen By BCC Enroll

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Giselle Sholler

Must not be taking: Immunosuppressants, Investigational drugs

Disqualifiers: Pregnancy, Breastfeeding, Mental illness, 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: 1

76 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing naxitamab with standard chemotherapy for high-risk neuroblastoma. Patients with a specific genetic change will also receive ceritinib. Naxitamab helps the immune system attack cancer, and ceritinib stops cancer cell growth. The goal is to improve survival rates for these patients.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any investigational drugs or immunosuppressive treatments (except local steroids) within 4 weeks before joining the trial.

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

Research shows that naxitamab, when combined with other treatments, can be effective for patients with high-risk neuroblastoma, especially when used early in treatment. In one study, patients receiving naxitamab-based therapy had improved long-term outcomes, with some achieving complete remission and better survival rates. ^{1 2 3 4 5}

Is naxitamab safe for humans?

Naxitamab has been studied in patients with high-risk neuroblastoma, and common side effects include pain, high blood pressure, and manageable allergic reactions. Serious side effects were rare, and the treatment was generally well-tolerated, even in young children. ^{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 specifically targeting GD2, a molecule found on neuroblastoma cells, and it is approved for outpatient use in combination with granulocyte-macrophage colony-stimulating factor. This allows for treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow, offering a novel approach compared to traditional chemotherapy. ^{1 2 3 4 5}

Research Team

Jaqueline Kraveka, DO

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

This trial is for children and young adults up to 21 years old with newly diagnosed high-risk neuroblastoma. Participants must have certain types of the disease, good liver and kidney function, and not be pregnant or breastfeeding. They should agree to use effective contraception if applicable. Those who've had previous systemic therapy beyond one cycle or are on immunosuppressants may not qualify.

Inclusion Criteria

My cancer was diagnosed at an advanced stage (INSS 2A/2B, 3, or 4).

My heart and liver are functioning well.

All subjects and/or legal guardians must sign informed written consent

Exclusion Criteria

Subjects receiving any investigational drug concurrently

I have not had systemic therapy, except in specific cases.

Pregnant or breastfeeding subjects

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive 5 cycles of multi-agent chemotherapy with naxitamab added to each cycle

Approximately 15 weeks

Naxitamab on Days 1, 3, and 5 of each cycle

Surgical Resection

Surgical resection of the primary tumor ideally occurs after the 4th cycle of Induction

1-2 weeks

Follow-up

Participants are monitored for disease response, event-free survival, overall survival, and toxicity

Up to 7 years

Treatment Details

Interventions

• Ceritinib
• Naxitamab

Trial Overview The study tests adding naxitamab to standard chemotherapy during the first five cycles of treatment for neuroblastoma. For patients with an ALK mutation, ceritinib will also be included once test results are available. The goal is to see if this combination improves response rates and survival compared to standard therapy alone.

Participant Groups

Group I: Subjects with ALK aberration Experimental Treatment 2 Interventions

5 cycles of standard of care induction + naxitimab + ceritinib Naxitimab on Days 1, 3, and 5 of each cycle Ceritinib once daily on every day of study

Group II: Subjects with ALK Wildtype or Unknown Experimental Treatment 1 Intervention

5 cycles of standard of care induction + naxitimab Naxitimab on Days 1, 3, and 5 of each cycle

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?

Giselle Sholler

Lead Sponsor

Trials

23

Recruited

2,500+

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Y-mAbs

Collaborator

Trials

1

Recruited

80+

Findings from Research

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]

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, 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]

References

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

Naxitamab: First Approval. [2021]

2. 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]

3. 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]

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

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

5. 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]