Hu3F8 + GM-CSF for Neuroblastoma

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Major organ dysfunction, Infection, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 10 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination treatment of the antibody Hu3F8 and the substance GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor) is safe for people with neuroblastoma, a cancer that begins in nerve tissue. It targets those whose neuroblastoma hasn't responded well to previous treatments or has returned after treatment. Suitable candidates for this trial include individuals with high-risk neuroblastoma, particularly those who have undergone intense treatments but still have cancer in their bone marrow or have experienced multiple relapses. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop any chemotherapy or immunotherapy at least three weeks before starting the study treatment. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

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

Research shows that using Hu3F8 and GM-CSF together is generally safe for treating neuroblastoma. Studies have found that Hu3F8 has low toxicity and does not cause strong immune reactions, allowing most patients to tolerate it well.

A thorough review of clinical data confirms the safety of GM-CSF. The FDA has already approved GM-CSF for use with another antibody treatment, suggesting it is likely well-tolerated by patients.

Overall, while some side effects might occur, past studies have found both Hu3F8 and GM-CSF to be safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neuroblastoma?

Researchers are excited about the treatment with Hu3F8 and GM-CSF for neuroblastoma because it offers a novel approach compared to the standard treatments like chemotherapy and radiation. Hu3F8 is a monoclonal antibody that specifically targets GD2, a molecule present on neuroblastoma cells, allowing for precise attack on cancer cells while sparing healthy ones. When combined with GM-CSF, which boosts the immune system, it potentially enhances the body's natural ability to fight the cancer. Unlike traditional options that have broad, non-specific mechanisms, this targeted therapy could lead to fewer side effects and improved outcomes for patients.

What evidence suggests that Hu3F8 combined with GM-CSF might be an effective treatment for neuroblastoma?

Research shows that Hu3F8, a specially designed antibody, has potential in treating neuroblastoma, a type of cancer. In this trial, participants will receive Hu3F8 combined with GM-CSF. Studies have found that Hu3F8, especially when used with interleukin-2 or GM-CSF, is generally well tolerated by patients with high-risk neuroblastoma. Another treatment, naxitamab, targets the same cancer marker and has been effective in treating neuroblastoma, suggesting that Hu3F8 could also be promising.

Using GM-CSF with antibodies like Hu3F8 may enhance the immune system's ability to fight cancer. Reviews emphasize the importance of GM-CSF in combination treatments to improve outcomes for high-risk neuroblastoma. Overall, these findings support the potential effectiveness of combining Hu3F8 with GM-CSF for treating neuroblastoma. ^{1 6 7 8 9}

Who Is on the Research Team?

Brian Kushner, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients over 1 year old with high-risk neuroblastoma, which hasn't responded to standard treatments or has come back. They must have a certain number of white blood cells and not be allergic to mouse proteins. Pregnant or breastfeeding women can't join, nor can those with major organ problems (except hearing loss) or active severe infections.

Inclusion Criteria

I am older than 1 year.

My neuroblastoma is not responding to initial treatments or has come back.

I have had treatments with specific antibodies and do not have HAHA antibodies.

Exclusion Criteria

Pregnant women or women who are breast-feeding.

My major organs are functioning well, except possible hearing loss or blood issues.

I have tested positive for HAHA antibodies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of iv hu3F8 in combination with sc GM-CSF over a treatment cycle of 10 days

10 days per cycle

3 visits (in-person) for hu3F8 administration

Expansion Phase II

Participants continue to receive treatment cycles every 1-2 months for up to 24 months or until 5 cycles post-major response

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• GM-CSF
• Hu3F8

Trial Overview The study tests the safety of combining an antibody called Hu3F8 with GM-CSF in treating neuroblastoma. It's looking at how well these two work together against cancer that's hard to treat or has returned after previous treatment.

How Is the Trial Designed?

Group I: expansion phase II single arm trial Experimental Treatment 1 Intervention

Group 1 patients have primary refractory disease (no prior relapse but incomplete response to treatment) in BM as documented by histology and/or 123\^I-MIBG scan. Group 2 patients are in \>2nd CR/VGPR and at high risk for another relapse. Group 3 patients have secondary refractory disease (prior relapse and incomplete response to retrieval therapy) in BM as documented by histology and/or 123\^I-MIBG scan. GM-CSF can be omitted if patients have a history of an allergy to GM-CSF or develop an allergic reaction to GM-CSF after initiating therapy while on the protocol.

Group II: Hu3F8 with GM-CSF Experimental Treatment 1 Intervention

The phase I single arm trial assesses escalating doses of iv hu3F8 (days 1, 3, 5) in the presence of sc GM-CSF (day -4 through 5). These 3 doses of hu3F8 and 10 days of GM-CSF constitute a treatment cycle. The expansion phase II single arm trial assesses the anti-NB activity of hu3F8+GM-CSF.in 3 groups of patients: Group 1 patients have primary refractory disease (no prior relapse but incomplete response to treatment) in BM as documented by histology and/or 123I-MIBG scan. Group 2 patients are in ≥2nd CR and at high risk for another relapse. Group 3 patients have secondary refractory disease (prior relapse and incomplete response to retrieval therapy) in BM as documented by histology and/or 123I-MIBG scan. Ph II: Groups 1 \& 3 pts can continue to get cycles every 1-2 months for up to 24 months from study enrollment or until they receive 5 cycles after a major response (CR or PR) is achieved.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Y-mAbs Therapeutics

Industry Sponsor

Trials

26

Recruited

1,600+

Published Research Related to This Trial

The study evaluated hu14.18-IL2 in 27 pediatric patients with recurrent neuroblastoma and found it can be safely administered at a maximum tolerated dose of 12 mg/m2/d, with reversible toxicities similar to those seen in adult studies.

While no complete or partial responses were observed, treatment led to immune activation, indicating potential antitumor activity, and a phase II trial is planned to further assess its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology Group. Osenga, KL., Hank, JA., Albertini, MR., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8416151/

Sargramostim (rhu GM-CSF) as Cancer Therapy (Systematic ... Sargramostim [recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF)] was approved by US FDA in 1991 to accelerate bone marrow recovery ...

2. partnertx.com partnertx.com/comprehensive-review-highlights-importance-of-leukine-in-combination-with-anti-gd2-immunotherapy-for-treatment-of-high-risk-pediatric-neuroblastoma/

Comprehensive Review Highlights Importance of Leukine ... The review provides a succinct summary of the mechanistic rationale and clinical data supporting the use of Leukine in combination with anti-GD2 mAbs.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38108214/

GM-CSF, G-CSF or no cytokine therapy with anti-GD2 ... This comprehensive review summarizes clinical data regarding efficacy and safety of GM-CSF, recombinant human granulocyte colony-stimulating factor (G-CSF) or ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01757626

NCT01757626 | Combination Therapy of Antibody Hu3F8 ... The purpose of this study is to find out if an antibody called Humanized 3F8 (Hu3F8) combined with granulocyte- macrophage colony stimulating factor (GM-CSF) is ...

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.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11703753/

GM-CSF, G-CSF, or No Cytokine Therapy with Anti-GD2 ... This comprehensive review summarizes clinical data regarding efficacy and safety of GM-CSF, recombinant human granulocyte colony-stimulating factor (G-CSF), or ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2059702922000801

How we approach the treatment of patients with high-risk ... Naxitamab in combination with sargramostim [recombinant granulocyte–macrophage colony-stimulating factor (GM-CSF)] was approved by the FDA in November 2020 ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ijc.34815

GM‐CSF, G‐CSF or no cytokine therapy with anti‐GD2 ... This comprehensive review summarizes clinical data regarding efficacy and safety of GM-CSF, recombinant human granulocyte colony-stimulating ...

9. semanticscholar.org semanticscholar.org/paper/Humanized-3F8-Anti-GD2-Monoclonal-Antibody-Dosing-A-Kushner-Cheung/fd50ea2137f680f24bc184f260dbf9a29fc9a24c

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; ...