Personalized DNA Vaccine for Pediatric Brain Tumor

Overseen By Andrew Cluster, 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

Trial Summary

What is the purpose of this trial?

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 returned or have been resistant to treatment.

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.

What data supports the effectiveness of the treatment Personalized neoantigen DNA vaccine, GNOS-PV02, for pediatric brain tumors?

Research shows that personalized neoantigen vaccines can generate strong immune responses in various cancers, including glioblastoma, a type of brain tumor. Additionally, the GNOS-PV02 vaccine showed a 25% response rate in patients with advanced liver cancer, suggesting potential effectiveness in other cancers. ^{1 2 3 4 5}

Is the personalized DNA vaccine safe for use in humans?

The personalized DNA vaccine, tested under various names, has shown a manageable safety profile in clinical trials for different cancers, including glioblastoma, melanoma, and hepatocellular carcinoma, with no serious treatment-related adverse events reported. ^{1 3 5 6 7}

How is the personalized DNA vaccine treatment for pediatric brain tumors different from other treatments?

The personalized DNA vaccine for pediatric brain tumors is unique because it targets neoantigens, which are specific to each patient's tumor, potentially enhancing the immune system's ability to recognize and attack cancer cells. This approach is different from standard treatments as it is tailored to the individual's tumor profile, aiming to generate a strong and specific immune response. ^{1 2 3 4 5}

Research Team

Andrew Cluster, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

I can care for myself but may need occasional help.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Personalized DNA Vaccine Immunogenic Against Melanoma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Extended treatment with MY-NEOVAX, personalized neoantigen-enhanced oncolytic viruses, for two end-stage cancer patients. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Personalized DNA Vaccine Tamps Down HCC. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Actively Personalized Neoantigen Vaccination in the Management of Newly Diagnosed Glioblastoma: A Systematic Review. [2022]

7. United States 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. [2023]