Naxitamab + Irinotecan + Temozolomide for Neuroblastoma

Recruiting at 1 trial location

Overseen By Steven DuBois, MD, MS

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Steven DuBois, MD

Must not be taking: Immunosuppressants, Glucocorticoids, Valproic acid, others

Disqualifiers: Pregnancy, CNS metastasis, Arrhythmias, others

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

Compensation: Varies

Number of Visits: 1

Duration: 18 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for neuroblastoma, a cancer that primarily affects children and young adults. Researchers aim to determine if administering the drug Naxitamab more slowly can reduce side effects. The trial also includes two chemotherapy drugs, Irinotecan and Temozolomide, along with Sargramostim, which boosts the immune system. Ideal participants have neuroblastoma that has returned or is not responding to treatment and have a measurable tumor or specific scan results. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination.

Do I need to stop taking my current medications to join the trial?

The trial requires that you stop taking certain medications before enrolling. You cannot be on immunosuppressive medications, certain anti-cancer agents, or specific drugs like valproic acid and strong CYP3A4 or UGT1A1 inhibitors within 14 days before joining. It's important to discuss your current medications with the trial team to ensure they don't interfere with the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown promising safety results for the combination of Naxitamab, Irinotecan, and Temozolomide. Naxitamab, a specially designed protein, is being tested for its effectiveness with these chemotherapy drugs. Research suggests that different chemotherapy combinations with Naxitamab can benefit patients with certain types of neuroblastoma, a cancer affecting nerve cells.

Naxitamab is generally well-tolerated, though some individuals may experience side effects such as mild to moderate fever, tiredness, or allergic reactions. Irinotecan and Temozolomide, common chemotherapy drugs, can cause side effects like nausea and reduced blood cell counts. Sargramostim, which strengthens the immune system, is also part of the treatment and usually has mild side effects.

Overall, early research considers the treatment safe. However, as this is an early-phase study, researchers are still determining the best way to administer Naxitamab to minimize side effects. Participants should consult their doctors to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Naxitamab, Irinotecan, and Temozolomide for neuroblastoma because it brings a new approach to tackling this aggressive cancer. Unlike traditional treatments that mainly use chemotherapy and radiation, this combination includes Naxitamab, a monoclonal antibody that specifically targets cancer cells, potentially improving precision and reducing damage to healthy cells. Additionally, integrating Sargramostim, a growth factor, could enhance the immune response, offering a holistic attack on the cancer. This combination aims to improve effectiveness while minimizing side effects, which is a promising development in the fight against neuroblastoma.

What evidence suggests that this trial's treatments could be effective for neuroblastoma?

Research has shown that the combination of naxitamab, irinotecan, and temozolomide, which participants in this trial will receive, may help treat neuroblastoma, a type of cancer. Studies have found that naxitamab-based therapy can work against neuroblastoma that doesn't respond to initial chemotherapy. In one study, this combination caused tumors to shrink in about 30% of patients. Naxitamab, a form of immunotherapy, has proven effective for patients with neuroblastoma in the bones or bone marrow. These findings suggest that this treatment could be a promising option for those whose neuroblastoma has returned or is difficult to treat. ^{1 2 3 4 5}

Who Is on the Research Team?

Steven DuBois, MD, MS

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with neuroblastoma that has come back or hasn't responded to treatment. Participants must meet certain health standards, but specific inclusion and exclusion criteria are not listed.

Inclusion Criteria

My condition has not improved after treatment.

Ability to comply with protocol requirements

Adequate contraception for participants with potential to become pregnant or impregnate a partner

Exclusion Criteria

Serious intercurrent illness

I stopped previous GD2 immunotherapy due to severe side effects, not including allergic reactions.

Prior allergic reaction to irinotecan or temozolomide

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Naxitamab, Irinotecan, Temozolomide, and Sargramostim in cycles to determine the safe infusion duration of Naxitamab

18 weeks

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Quarterly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Irinotecan
• Naxitamab
• Temozolomide

Trial Overview The study tests a combination of chemotherapy drugs (Irinotecan and Temozolomide), a bone marrow stimulant (Sargramostim), and an immunotherapy drug (Naxitamab) to see if slow administration of Naxitamab reduces side effects in relapsed/refractory neuroblastoma.

How Is the Trial Designed?

Group I: Naxitamab Infusion+ Ironotecan + Temozolomide + Sargramostim Experimental Treatment 4 Interventions

Participants will be enrolled in a modified 3+3 design to establish a maximum tolerated, infusion duration for Naxitamab. Dosage will start at Duration Level 1 and will de-escalate to Duration Level -1 or escalate to Duration Level 2 according to dose-limiting toxicity (DLT) criteria. * Baseline visit * Cycle 1 (21 day cycle): * Days 1, 3, and 5: Predetermined dose of Naxitamab 1x daily * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 through 5: Predetermined dose of Ironotecan 1x daily * Days 6 through 12: predetermined dose of Sargramostim 1x daily * Cycles 2 through 6 (21 day cycles): * Imaging on Cycles 2, 4, and 6 * Days 1, 3, and 5: Predetermined dose of Naxitamab 1x daily * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 through 5: Predetermined dose of Ironotecan 1x daily * Days 6 through 12: predetermined dose of Sargramostim 1x daily * End of treatment visit * Follow up at 1 year post-treatment

Who Is Running the Clinical Trial?

Steven DuBois, MD

Lead Sponsor

Y-mAbs Therapeutics

Industry Sponsor

Trials

26

Recruited

1,600+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.10039

Irinotecan, temozolomide and naxitamab plus GM-CSF ... Our clinical trial results suggest different chemotherapy combinations with naxitamab have the potential to rescue patients with R/R HR-NB.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10571514/

Early Salvage Chemo-Immunotherapy with Irinotecan, ... In summary, naxitamab-based chemo-immunotherapy is effective against primary chemo-resistant neuroblastoma, significantly improving long-term ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07027748

NCT07027748 | Feasibility Study of Prolonged ... This research is being done to investigate a treatment regimen of Irinotecan, Temozolomide, and Sargramostin, and an immunotherapy called Naxitamab.

4. asco.org asco.org/abstracts-presentations/ABSTRACT449924

Naxitamab chemo-immunotherapy regimens other than ... Out of the 30 treatments, 5 achieved complete response (CR), 2 partial response (PR), and 2 mixed response (MR), providing an objective response (OR) of 30%.

5. 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.