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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine designed to help the immune system target and destroy brain tumor cells in individuals with H3 G34-mutant diffuse hemispheric glioma. The main goal is to assess the vaccine's safety and determine the optimal dose. This study includes individuals diagnosed with this specific brain tumor type who have recovered from recent surgeries or biopsies. Participants will undergo blood and stool tests, along with regular MRIs, to help researchers evaluate the treatment's effectiveness. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

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

Research shows that vaccines like the neoantigen-targeted ppDC have the potential to be safe and well-tolerated for certain brain tumors. Previous studies on similar personalized vaccines indicate they are generally safe and can trigger a strong immune response in patients, suggesting the body is likely to respond well without serious side effects.

Since this is an early stage of testing for the neoantigen-targeted ppDC vaccine, the main goal is to learn more about its safety and any possible side effects. Researchers are closely monitoring how the vaccine affects the body. While there is hope based on similar treatments, this trial will provide more specific safety information for the H3 G34-mutant diffuse hemispheric glioma condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain tumors, which often include surgery, radiation, and chemotherapy, the Neoantigen-Targeted ppDC Vaccine offers a new approach by harnessing the body's immune system. This vaccine targets specific neoantigens—unique markers found on tumor cells—training the immune system to recognize and attack the cancer more precisely. Additionally, it is combined with poly ICLC, an immune booster, to enhance the body's response. Researchers are excited about this treatment because it represents a personalized and potentially less toxic option, aiming to provide targeted action against brain tumors with fewer side effects.

What evidence suggests that this vaccine might be an effective treatment for brain tumors?

Research has shown that personalized vaccines, such as the neoantigen-targeted ppDC vaccine, can effectively boost the immune system in patients with glioblastoma, a type of brain tumor. In this trial, participants will receive the ppDC vaccine combined with Poly ICLC. This vaccine uses the patient's own white blood cells to help the body identify and attack tumor cells. Studies have demonstrated that dendritic cells, special immune cells, effectively strengthen the body's defense against brain cancers. By targeting specific changes in the tumor, like the H3 G34 mutation in diffuse hemispheric glioma, the vaccine aims to enhance the body's ability to fight the tumor. Initial findings suggest this approach could be safe and may help in treating certain brain tumors. ^{2 6 7 8 9}

Who Is on the Research Team?

Anthony C. Wang

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. uclahealth.org uclahealth.org/clinical-trials/vaccine-neoantigen-targeted-ppdc-treatment-h3-g34-mutant

A Vaccine (Neoantigen-Targeted ppDC) for the Treatment ... Giving neoantigen-targeted ppDC may be safe, tolerable and/or effective in treating patients with diffuse hemispheric glioma with a H3 G34 mutation.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06342908

NCT06342908 | A Vaccine (Neoantigen-Targeted ppDC) ... Giving neoantigen-targeted ppDC may be safe, tolerable and/or effective in treating patients with diffuse hemispheric glioma with a H3 G34 mutation.

3. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/glioma

UCLA Glioma Clinical Trials for 2025 — Los Angeles 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- ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12314604/

Advancing vaccine-based immunotherapy in glioblastoma ... DCs have been a major target in neoantigen and/or mRNA vaccine research for brain cancer because of their efficacy in stimulating immunity and the precedent of ...

5. withpower.com withpower.com/trial/vaccine-for-brain-tumor-fb4bb

Vaccine for Brain Tumor Research shows that neoantigen-based personalized vaccines have been effective in generating strong immune responses in patients with glioblastoma, a type of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06342908

NCT06342908 | A Vaccine (Neoantigen-Targeted ppDC ... Giving neoantigen-targeted ppDC may be safe, tolerable and/or effective in treating patients with diffuse hemispheric glioma with a H3 G34 mutation. Detailed ...

7. clinicaltrials.ucbraid.org clinicaltrials.ucbraid.org/glioma

University of California Health Glioma Clinical Trials for 2025 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- ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06342908?cond=%22Glioma%22&intr=%22Cathartics%22&viewType=Table&rank=3

A Vaccine (Neoantigen-Targeted ppDC) for the Treatment ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8427683/

Efficacy and Safety of Actively Personalized Neoantigen ... Actively personalized vaccines aimed at unmutated peptides and neoantigens for patients with GBM are safe and highly immunogenic, particularly when ...