Naxitamab for High-Risk Neuroblastoma

Recruiting at 24 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

93 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of naxitamab (Danyelza) when added to standard chemotherapy for those newly diagnosed with high-risk neuroblastoma, a cancer primarily affecting children. The researchers aim to determine if naxitamab can improve response and survival rates. The treatment includes naxitamab with five cycles of standard chemotherapy. Suitable candidates for this trial are those with high-risk neuroblastoma, identified by specific medical features like certain genetic markers. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, contributing to important advancements in cancer treatment.

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.

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

Research has shown that naxitamab is generally well-tolerated by patients with neuroblastoma, a type of cancer. In earlier studies, naxitamab provided significant benefits for patients whose neuroblastoma was not cured by previous treatments. These studies found that the side effects of naxitamab were manageable and not too severe compared to the potential benefits of the treatment.

The FDA has already approved naxitamab for use in other neuroblastoma cases, indicating its safety for treating this cancer. While any treatment can have side effects, current evidence suggests that naxitamab could be a safe option for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for neuroblastoma?

Naxitamab is unique because it specifically targets GD2, a molecule found on the surface of neuroblastoma cells, making it a precise weapon against the disease. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, naxitamab hones in on cancer cells, potentially reducing damage to healthy cells. Moreover, it is designed to be administered in conjunction with standard treatment cycles, providing a synergistic effect that could enhance overall effectiveness and offer hope for better outcomes in high-risk neuroblastoma patients. Researchers are excited about naxitamab's potential to improve survival rates and reduce side effects compared to existing therapies.

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

Research has shown that naxitamab, which participants in this trial will receive, works well against high-risk neuroblastoma, especially when the cancer resists chemotherapy. Studies have found that adding naxitamab to treatment can greatly improve survival rates. In earlier trials, patients who received naxitamab had a 73% chance of remaining free from cancer events and a 93% chance of overall survival over three years. These findings indicate that naxitamab can lead to better outcomes for patients with high-risk neuroblastoma. ^{2 6 7 8 9}

Who Is on the Research Team?

Jaqueline Kraveka, DO

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: HRNB Newly diagnosed subjects 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 Therapeutics

Industry Sponsor

Trials

26

Recruited

1,600+

Y-mAbs

Collaborator

Trials

1

Recruited

80+

Published Research Related to This Trial

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]

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]

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]

Citations

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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 ...

2.

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 ...

3.

nature.com

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

The anti-GD2 monoclonal antibody naxitamab plus GM ...

Naxitamab-related Grade 3 adverse events included hypotension (58%) and pain (54%). Overall, naxitamab demonstrated clinically meaningful ...

4.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2020/761171Orig1s000MultidisciplineR.pdf

761171Orig1s000 - accessdata.fda.gov

effectiveness of naxitamab have been established in pediatric patients with high-risk neuroblastoma based on results from clinical trials in ...

5.

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 ...

Patients with HR-NB treated in first CR with naxitamab + GM-CSF achieved encouraging survival rates, with 36-month EFS 73% and OS 93%. Outcome cannot be ...

6.

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 ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01662804

Humanized 3F8 Monoclonal Antibody (Hu3F8) When ...

The purpose of this study is to find out if "humanized 3F8" (Hu3F8) when combined with interleukin-2 (rIL2) is safe for treating neuroblastoma and other ...

8.

jamanetwork.com

jamanetwork.com/journals/jamaoncology/fullarticle/2703119

Humanized 3F8 Anti-GD2 Monoclonal Antibody Dosing ...

This phase 1 clinical trial found hu3F8 to be associated with modest toxic effects, low immunogenicity, and substantial antineuroblastoma activity.

9.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.10024

High-dose naxitamab plus stepped-up dosing of GM-CSF ...

Naxitamab+GM-CSF is effective against chemoresistant NB in BM, supporting further development of naxitamab which is proceeding in a pivotal international trial.