N-803 Combination Therapy for Neuroblastoma

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: Pregnancy, HIV, Hepatitis, 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

Compensation: Varies

Number of Visits: 11

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination treatment for individuals with neuroblastoma, a cancer affecting nerve tissue. It targets those whose cancer did not fully respond to previous treatments or has recurred. Researchers aim to determine if adding N-803, an experimental treatment, to a mix of other cancer treatments is safe and more effective. The trial seeks participants with high-risk neuroblastoma that is difficult to treat or has returned after initial treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

The trial requires that you stop taking certain medications before joining. You must not take other anti-cancer agents, certain steroids, or drugs that affect specific liver enzymes (CYP3A4 and CYP2B6) within a specified time before starting the trial. It's best to discuss your current medications with the trial team to see if any need to be stopped.

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

Research shows that N-803, when combined with chemoimmunotherapy, is being tested for safety in children with relapsed or hard-to-treat neuroblastoma. Earlier studies found that N-803 can be safely combined with chemotherapy and immunotherapy in similar cases. These studies have demonstrated that this combination enhances the ability of natural killer cells (a type of immune cell) to attack cancer cells more effectively.

Regarding side effects, the combination has generally been well-tolerated. Some patients experienced side effects, but these were manageable. The trial is in phase 2, indicating that initial safety checks have been positive enough to continue testing.

Overall, while more research is needed to fully understand the safety, early results are promising for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about N-803 for neuroblastoma because it introduces a novel approach by combining immunotherapy with chemotherapy. Unlike traditional treatments that mainly focus on chemotherapy, this therapy includes N-803, an engineered form of interleukin-15 (IL-15), which boosts the immune system's ability to fight cancer cells. This combination aims to enhance the effectiveness of the existing chemoimmunotherapy regimen, potentially leading to better outcomes for patients. By targeting the immune system, N-803 could provide a more robust and sustained response against neuroblastoma compared to standard options.

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

Research shows that N-803 might help treat neuroblastoma, a type of cancer. Studies indicate that N-803 boosts the activity and growth of certain immune cells, crucial for fighting cancer. In this trial, some participants will receive chemoimmunotherapy plus N-803, while others will receive chemoimmunotherapy alone. Early results suggest that combining N-803 with other treatments can greatly enhance the body's ability to target and fight neuroblastoma cells. Overall, the evidence is promising and supports the potential of N-803 in treating this challenging condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Sara Federico, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for patients with neuroblastoma that hasn't responded to previous treatments or has come back after treatment. Participants must meet certain health criteria not specified here.

Inclusion Criteria

My neuroblastoma is classified as high-risk.

I can do most activities but may need help.

I have had anti-GD2 treatment without my cancer getting worse during the treatment.

Exclusion Criteria

Pregnancy, breast feeding, or unwillingness to use effective contraception during the study

Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Patients who have undergone a prior allogeneic stem cell or solid organ transplant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-In

Initial safety assessment with irinotecan, temozolomide, hu14.18K322A, GM-CSF, and N-803 to evaluate feasibility and tolerability

3 weeks

1 cycle (21 days)

Phase 2 Treatment

Randomized treatment with chemoimmunotherapy alone or with N-803

Up to 30 weeks

Up to 10 cycles (21 days each)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• N803

Trial Overview The study tests if adding N-803 to a mix of drugs (irinotecan, temozolomide, hu14.18K322A, and GM-CSF) is safe and works better for treating relapsed/refractory neuroblastoma than the drug combo alone.

How Is the Trial Designed?

Group I: Safety Run-In Treatment Schedule - Chemoimmunotherapy + N-803 Experimental Treatment 5 Interventions

The first 6 patients included in the safety assessment run-in phase will receive cycles of irinotecan, temozolomide, hu14.18K322A, GM-CSF and N-803. If fewer than 2 patients in the first cohort of 6 patients experience a DLT in Cycle 1, then the trial will proceed to Phase 2. If 2 or more of the first 6 patients experience a DLT in Cycle 1 then the N-803 will be dose reduced to 15 mcg/kg and 6 more patients will be enrolled in the safety assessment run-in. Once the safety assessment run-in phase is completed, patients will be enrolled onto the phase 2 study.

Group II: Chemoimmunotherapy + N-803 Experimental Treatment 5 Interventions

Patients will be randomized to receive chemoimmunotherapy plus N-803.

Group III: Chemoimmunotherapy Experimental Treatment 4 Interventions

Patients will be randomized to receive chemoimmunotherapy alone.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2950329924000626

Efficiently targeting neuroblastoma with the combination of ... In this study, we investigated the in-vitro and in-vivo anti-tumor effects of anti-ROR1 CAR exPBNK cells with or without N-803 against ROR1 + NB models.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8268924/

Combinatorial immunotherapy of N-803 (IL-15 ... 21 Consistent with those results, our data shows that N-803 significantly stimulated the proliferation of exPBNK cells (figure 1A, B). NK ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07085338

NCT07085338 | A Phase II Study With a Safety Run-In of ... This is a randomized phase 2 study with a safety assessment run-in conducted in children with relapsed or refractory neuroblastoma to evaluate the feasibility, ...

4. astctjournal.org astctjournal.org/article/S2666-6367(23)02296-0/fulltext

IL15 (N-803) and IL21 (oHSV-21) Significantly Enhance ... Our data demonstrated IL15 or IL21 based novel cytokine therapy (N-803 or C021) significantly enhanced the anti-tumor efficacy of ROR1 CAR NK targeting NB ...

5. jitc.bmj.com jitc.bmj.com/content/10/Suppl_2/A918

881 Significant therapeutic effects of anti-ROR1 CAR NK ... Conclusions Our data demonstrate the significant anti-tumor efficacy of combining C021 with anti-ROR1 CAR-exPBNKs to therapeutically target NB ...

6. stjude.org stjude.org/care-treatment/clinical-trials/hunb803-neuroblastoma.html

N-803 Plus Chemoimmunotherapy for Neuroblastoma In this study, HuNB803, doctors will see if N-803 can be given safely with chemotherapy plus immunotherapy to children with relapsed and refractory ...

7. link.springer.com link.springer.com/article/10.1007/s10555-024-10212-8

Natural killer cells in neuroblastoma: immunological ... This review outlines the mechanisms employed by NK cells to recognize and eliminate malignant cells, delving into the dynamic relationship between ligand- ...