Personalized DNA Vaccine for Pediatric Brain Tumor

Recruiting at 1 trial location

Overseen By Michael A Huang, M.D.

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Strong CYP3A4 inhibitors

Disqualifiers: Other malignancy, Uncontrolled illness, Autoimmune condition, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

7 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and feasibility of a new personalized DNA vaccine for treating brain tumors in young people. It focuses on patients whose tumors have returned or resist standard treatments. Participants will receive a vaccine tailored to their tumor's unique characteristics. The trial seeks individuals aged 12 to 25 with a recurrent or hard-to-treat brain tumor who have already undergone standard treatment. 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 innovative therapy.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for some treatments before starting the vaccine. For example, you must stop myelosuppressive chemotherapy at least 3 weeks before, and biologic agents at least 7 days before the first vaccine dose. It's best to discuss your specific medications with the study team.

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

Research has shown that personalized neoantigen DNA vaccines are generally safe in clinical trials for various cancers, including glioblastoma, a type of brain cancer. Mid-term results from one study indicated that patients tolerated the vaccine well, experiencing no severe side effects. However, none of the patients experienced tumor shrinkage or disappearance, and the average time patients lived without disease progression was 1.9 months.

While these findings suggest the vaccine is generally safe, it's important to note that this trial is in its early stages. Early trials primarily focus on assessing safety and side effects, so more research is needed to understand long-term patient responses to the vaccine. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pediatric brain tumors, which typically involve surgery, radiation, and chemotherapy, this personalized DNA vaccine is designed to target the unique makeup of a patient's tumor. Researchers are excited because the vaccine introduces a new mechanism of action by using neoantigens—specific markers on cancer cells—to stimulate the immune system to attack the tumor more precisely. Additionally, the vaccine is tailored to each patient's tumor, potentially increasing effectiveness and reducing side effects compared to more generalized treatments. This personalization and innovative approach could improve outcomes and offer new hope for patients with these challenging conditions.

What evidence suggests that this personalized DNA vaccine could be effective for pediatric brain tumors?

Research has shown that personalized DNA vaccines, like the one tested in this trial, have been generally safe in trials for various cancers, including brain tumors such as glioblastoma. Although early study results did not show significant tumor shrinkage, patients tolerated the vaccines well. This trial aims to identify specific markers on cancer cells, called neoantigens, which these vaccines can target. Early signs suggest this method might help the immune system attack the cancer. While still in the early stages, this strategy builds on encouraging data from similar treatments in the lab. ^{1 2 3 4 6}

Who Is on the Research Team?

Michael A Huang, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for young people aged 12-39 with recurrent or resistant pediatric brain tumors. They must have had standard care for their tumor, tissue available for sequencing, and be able to consent. Excluded are those recently vaccinated (except COVID-19), pregnant/breastfeeding individuals, certain medical conditions, recent other immunotherapies or investigational agents, allergies to vaccines, uncontrolled illnesses/infections, immunodeficiency disorders/autoimmune conditions on therapy.

Inclusion Criteria

Life expectancy > 24 weeks

My blood counts and organ functions are within normal ranges.

I am taking Bevacizumab to control swelling in my brain and reduce my need for high doses of steroids.

Exclusion Criteria

I do not have any severe illnesses that would stop me from following the study's requirements.

My screening did not identify any targetable cancer markers.

I haven't had cancer, except for certain types, in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Priming Treatment

Participants receive the personalized neoantigen DNA vaccine monthly for 6 doses

6 months

6 visits (in-person)

Booster Treatment

Participants receive booster injections quarterly if sufficient quantities of vaccine are available

Up to 1 year

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Personalized neoantigen DNA vaccine

Trial Overview The study tests the safety and feasibility of a personalized DNA vaccine designed based on each patient's unique tumor characteristics using Ichor TDS-IM v2.0 after a blood draw. The goal is to see if this approach can help treat children and young adults whose brain tumors have not responded well to previous treatments.

How Is the Trial Designed?

Group I: Personalized neoantigen DNA vaccine Experimental Treatment 3 Interventions

Patients will receive the vaccine monthly (+/- 3 days) for 6 doses as a priming phase followed by booster injections quarterly Q3mo thereafter. If sufficient quantities of vaccine are available, vaccination may continue until development of intolerance or disease progression in the case of fatal high grade neoplasms or for up to one year. Additionally, patients with non-fatal tumors who complete one year of vaccinations and have stable disease at the completion of treatment will be given the option of resuming vaccinations if they develop subsequent progression.

Personalized neoantigen DNA vaccine is already approved in United States for the following indications:

Approved in United States as GNOS-PV02 for:

• Pediatric recurrent brain tumors

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Children's Discovery Institute

Collaborator

Trials

4

Recruited

430+

Children's Discovery Institute

Collaborator

Trials

6

Recruited

540+

Published Research Related to This Trial

The personalized neoantigen vaccine EVX-02 demonstrated strong and durable T-cell responses in melanoma patients following surgery, indicating its potential effectiveness in cancer immunotherapy.

The promising results from EVX-02 have led to the development of a next-generation vaccine, EVX-03, which features an enhanced antigen-selection process and an additional payload to potentially improve its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized DNA Vaccine Immunogenic Against Melanoma. [2023]

A personalized synthetic long peptide vaccine targeting neoantigens was successfully developed and tested in a patient with glioblastoma (GBM), showing the ability to elicit specific T cell responses post-vaccination.

The study indicates that neoantigen-based vaccines can be a feasible and promising therapeutic strategy for treating lower mutational burden tumors like GBM, as evidenced by the detection of immune responses in both peripheral blood and tumor-infiltrating lymphocytes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma. Johanns, TM., Miller, CA., Liu, CJ., et al.[2021]

Personalized neoantigen vaccination is a feasible strategy for treating glioblastoma, even in tumors with low mutation loads and an immunologically 'cold' environment, as demonstrated in a phase I/Ib study.

Patients who did not receive dexamethasone showed enhanced immune responses, including increased neoantigen-specific T cells that can migrate into glioblastoma tumors, suggesting that this vaccination approach could improve the immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Keskin, DB., Anandappa, AJ., Sun, J., et al.[2023]

In a phase I/II trial involving patients with advanced hepatocellular carcinoma, the personalized DNA vaccine GNOS-PV02, when combined with pembrolizumab and plasmid-encoded IL12, achieved a response rate of 25%.

The vaccine was designed to target up to 40 unique neoantigens specific to each patient and demonstrated a manageable safety profile, indicating it could be a promising treatment option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized DNA Vaccine Tamps Down HCC. [2022]

The personalized neoantigen-based vaccine NEO-PV-01, combined with PD-1 blockade, was found to be safe in a phase Ib trial involving 82 patients with advanced melanoma, lung, or bladder cancer, with no serious treatment-related adverse events reported.

The vaccine successfully induced strong CD4+ and CD8+ T cell responses, which not only targeted the specific neoantigens but also led to an immune response against additional neoantigens, indicating a broadening of the immune attack on the tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer. Ott, PA., Hu-Lieskovan, S., Chmielowski, B., et al.[2023]

Personalized neoantigen-enhanced oncolytic adenoviruses, specifically MY-NEOVAX™, showed positive therapeutic effects in two heavily pretreated end-stage cancer patients, indicating potential for improved treatment outcomes.

Both patients experienced treatment benefits lasting over 12 months without significant toxicities or serious adverse events, along with documented stabilization of their tumors and improved overall health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended treatment with MY-NEOVAX, personalized neoantigen-enhanced oncolytic viruses, for two end-stage cancer patients. Bouvet, M., Reid, TR., Larson, C., et al.[2020]

Neoantigen-based personalized vaccines for glioblastoma (GBM) have shown high immunogenicity and safety in clinical trials, with significant T cell responses observed in most patients.

In a review of two trials involving 24 patients, no serious treatment-related adverse events were reported, indicating that these vaccines could be a promising treatment option for newly diagnosed GBM, although larger studies are needed to confirm their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Actively Personalized Neoantigen Vaccination in the Management of Newly Diagnosed Glioblastoma: A Systematic Review. Khan, M., Li, X., Yan, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12407177/

Neoantigen-driven personalized tumor therapy: An update ... Mid-term phase I results showed good vaccine tolerability; however, the overall response rate was 0%, with a median progression-free survival (PFS) of 1.9 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03988283

NCT03988283 | Neoepitope-based Personalized DNA ... The purpose of this research study is to learn about the safety and feasibility of giving a personalized DNA vaccine to people with brain tumors that have ...

3. withpower.com withpower.com/trial/phase-1-brain-neoplasms-9-2021-52548

Personalized DNA Vaccine for Pediatric Brain Tumor The personalized DNA vaccine, tested under various names, has shown a manageable safety profile in clinical trials for different cancers, including glioblastoma ...

4. academic.oup.com academic.oup.com/neuro-oncology/article/26/Supplement_4/0/7694687

Neuro-Oncology | Oxford Academic We anticipate the identification of actionable neoantigens in pediatric brain tumors to support the potential efficacy of personalized DNA ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8034661/

Therapeutic cancer vaccines for pediatric malignancies Though there are no current ongoing clinical trials, there are promising preclinical data to suggest that viral-based vaccines may be effective in brain tumors.

6. nature.com nature.com/articles/s41591-024-02894-y

Personalized neoantigen vaccine and pembrolizumab in ... Safety and immunogenicity were assessed as primary endpoints, and treatment efficacy and feasibility were evaluated as secondary endpoints. The ...