Vaccine for Brain Tumor

Overseen By Sichen Li

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids, Live vaccines, others

Disqualifiers: Age, Pregnancy, Autoimmune, Infections, 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

Duration: 6 months

6 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you have received prior systemic anti-cancer therapy within 2 weeks before enrollment or if you are on certain immunosuppressive therapies.

What data supports the effectiveness of the treatment Neoantigen-Targeted ppDC Vaccine for brain tumors?

Research shows that neoantigen-based personalized vaccines have been effective in generating strong immune responses in patients with glioblastoma, a type of brain tumor. These vaccines have been shown to be safe and capable of activating T cells (a type of immune cell) to target and potentially fight the tumor. ^{1 2 3 4 5}

Is the Neoantigen-Targeted ppDC Vaccine safe for humans?

Research shows that neoantigen-based personalized vaccines, including the Neoantigen-Targeted ppDC Vaccine, have been tested in various cancers like glioblastoma and melanoma and are generally considered safe, with no serious treatment-related side effects reported. ^{1 2 4 5 6}

How is the Neoantigen-Targeted ppDC Vaccine treatment different from other treatments for brain tumors?

The Neoantigen-Targeted ppDC Vaccine is unique because it uses personalized neoantigens (specific proteins from a patient's tumor) to stimulate the immune system, specifically targeting the tumor cells. This approach is different from standard treatments as it aims to generate a strong immune response by activating T cells (a type of immune cell) to recognize and attack the tumor, offering a tailored and potentially more effective treatment for glioblastoma, a common and aggressive brain tumor. ^{1 2 3 4 7}

What is the purpose of this trial?

This phase I trial tests the safety and side effects, and best dose of a vaccine (neoantigen-target ppDC) in treating patients with H3 G34-mutant diffuse hemispheric glioma. Vaccines made from the patient's own white blood cells and peptide-pulsed dendritic cells may help the body build an effective immune response to kill tumor cells. Giving neoantigen-targeted ppDC may be safe, tolerable and/or effective in treating patients with diffuse hemispheric glioma with a H3 G34 mutation.

Research Team

Anthony C. Wang

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

This trial is for patients with a specific brain tumor known as H3 G34-mutant diffuse hemispheric glioma. Participants should be suitable for vaccine therapy from their own white blood cells and have tumors that can be measured by MRI.

Inclusion Criteria

It has been more than 14 days since my last stereotactic biopsy.

I am able to care for myself but may not be able to do active work.

My liver function tests are within the required range.

Exclusion Criteria

I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

I've had cancer treatment within the last 2 weeks and have recovered from side effects.

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Leukapheresis

Patients undergo leukapheresis 10 days prior to first injection

1 week

1 visit (in-person)

Treatment

Patients receive ppDC intradermally with poly ICLC intramuscularly every 2 weeks for 3 doses, then every 6 months for up to 3 doses

6 months

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

2 visits (in-person) at 30 and 120 days, then periodic monitoring

Treatment Details

Interventions

• Neoantigen-Targeted ppDC Vaccine

Trial Overview The study is testing the safety, side effects, and best dose of a personalized vaccine made from the patient's dendritic cells designed to target tumor cells in those with certain brain tumors.

Participant Groups

Group I: Treatment (PpDC vaccine, Poly ICLC) Experimental Treatment 5 Interventions

Patients undergo leukapheresis 10 days prior to first injection. Patients then receive ppDC ID with poly ICLC IM in both arms Q2W for total 3 doses and then every 6 months for up to 3 doses. Patients undergo MRI throughout the trial. Patients also undergo blood sample collection throughout the trial in addition to stool sample collection during screening and on the trial.

Neoantigen-Targeted ppDC Vaccine is already approved in United States for the following indications:

Approved in United States as Neoantigen-Targeted ppDC Vaccine for:

• H3 G34-mutant diffuse hemispheric glioma

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Findings from Research

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]

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]

Dendritic cell (DC) vaccines loaded with personalized neoantigens have shown promise as safe and effective cancer treatments, particularly for melanoma and glioblastoma, by activating immune responses against tumors.

Hundreds of clinical trials are ongoing worldwide, demonstrating the stability and reliability of DC vaccines, although challenges remain in maximizing their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized Neoantigen-Pulsed DC Vaccines: Advances in Clinical Applications. Tang, L., Zhang, R., Zhang, X., et al.[2021]

Neoantigen-based cancer vaccines are showing promise in targeting unique mutations in individual tumors, which could enhance the immune system's ability to fight cancer.

These vaccines are currently being tested in clinical trials, highlighting their potential despite challenges in manufacturing and the need for further research to optimize their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personal neoantigen cancer vaccines: The momentum builds. Fritsch, EF., Hacohen, N., Wu, CJ.[2021]

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]

Cancer neoantigens, which are unique proteins produced by genetic changes in tumors, are promising targets for immunotherapy, particularly through neoantigen vaccines designed to stimulate the immune system while reducing the risk of autoimmune reactions.

Current neoantigen vaccine platforms, including synthetic long peptides, RNA, dendritic cells, and DNA vaccines, show early promise in clinical trials, but challenges remain in identifying effective neoantigens and overcoming the immunosuppressive environment of tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoantigen vaccine platforms in clinical development: understanding the future of personalized immunotherapy. Supabphol, S., Li, L., Goedegebuure, SP., et al.[2022]

References

1. 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]

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

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

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

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Personalized Neoantigen-Pulsed DC Vaccines: Advances in Clinical Applications. [2021]

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

Personal neoantigen cancer vaccines: The momentum builds. [2021]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

Neoantigen vaccine platforms in clinical development: understanding the future of personalized immunotherapy. [2022]