Personalized DNA Vaccine for Glioblastoma

Not currently recruiting at 1 trial location

Overseen By Tanner M Johanns, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Immunotherapy, Investigational agents

Disqualifiers: Other malignancy, Immunodeficiency, Autoimmune, 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: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new personalized DNA vaccine designed to treat glioblastoma, an aggressive brain cancer. The main goal is to determine if this vaccine is safe and can trigger an immune response in patients. Participants will receive the vaccine alongside standard radiation therapy. The trial seeks individuals recently diagnosed with a specific type of glioblastoma who have not previously undergone immunotherapy. As a Phase 1 trial, this 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 does not specify if you need to stop taking your current medications. However, systemic corticosteroid therapy is allowed if the dose is no greater than 4 mg per day, and Bevacizumab is permitted for certain conditions. It's best to discuss your specific medications with the trial 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 for people. These vaccines target specific markers on tumors, called neoantigens, and patients with glioblastoma tolerate them well. Serious side effects rarely occur, with most people experiencing only mild reactions, such as soreness at the injection site or mild flu-like symptoms.

For instance, one study found that the vaccine was safe and triggered a strong immune response in patients. This indicates that the body recognized and reacted to the cancer cells, a positive sign that the treatment is working as intended.

Overall, while more research is needed to fully understand the long-term effects, early data appears promising for the safety of these vaccines in people with glioblastoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the personalized neoantigen DNA vaccine for glioblastoma because it offers a tailored approach to cancer treatment. Unlike standard treatments like surgery, chemotherapy, and radiation, which target cancer more generally, this vaccine is designed to stimulate the immune system to specifically recognize and attack the unique mutations present in an individual's tumor. This precision targeting could potentially lead to more effective treatment outcomes with fewer side effects. Additionally, the use of DNA technology in the vaccine allows for rapid customization, making it a cutting-edge option in the fight against this aggressive brain cancer.

What evidence suggests that this personalized neoantigen DNA vaccine might be an effective treatment for glioblastoma?

This trial will evaluate a personalized DNA vaccine for glioblastoma. Studies have shown that personalized DNA vaccines can trigger strong immune responses in patients with this type of brain cancer. These vaccines target specific markers on tumor cells, helping the body recognize and attack them. Research indicates these vaccines are safe and may slow tumor growth. Early trials in patients showed promising results, with some experiencing improved outcomes. Overall, these vaccines offer hope for more effective treatments against glioblastoma. ^{1 3 4 6 7}

Who Is on the Research Team?

Tanner M Johanns, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed, unmethylated glioblastoma who've had a craniotomy or resection. Participants must consent to genome sequencing and agree to use contraception. They should have normal organ function, not be on high-dose steroids, and can't have other cancers within the last 3 years or any immune system disorders.

Inclusion Criteria

Patients who had prior craniotomy with biopsy, subtotal resection, total gross resection, or re-resection will be permitted.

Consent to genome sequencing and dbGaP-based data sharing and has provided or will provide germline (PBMC) and tumor DNA/RNA samples of adequate quality for sequencing. (Acquisition of specimens for sequencing and the sequencing itself may be done as part of routine care or another research project.)

Normal bone marrow and organ function as defined below:

Exclusion Criteria

No candidate neoantigen identified during screening.

Inadequate tissue acquisition to allow for neoantigen screening.

Known allergy, or history of serious adverse reaction to, vaccines such as anaphylaxis, hives, or respiratory difficulty.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Standard radiation therapy administered per standard of care

Treatment

Participants receive GNOS-PV01 + INO-9012 on Days 1, 22, and 43 of Cycle 1 and then on Day 1 of each subsequent cycle

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Personalized neoantigen DNA vaccine

Trial Overview The study tests a personalized neoantigen-based DNA vaccine using the CELLECTRA®2000 EP Device in patients with glioblastoma. It aims to assess safety and how well it triggers an immune response against the cancer.

How Is the Trial Designed?

Group I: Vaccine (GNOS-PV01 + INO-9012) Experimental Treatment 3 Interventions

* Standard radiation therapy will be administered per standard of care and is outside the scope of this study. * GNOS-PV01 + INO-9012 will be given on Days 1, 22, and 43 of Cycle 1 and then on Day 1 of each subsequent cycle beginning with Cycle 2.

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+

Geneos Therapeutics

Industry Sponsor

Trials

2

Recruited

50+

The Foundation for Barnes-Jewish Hospital

Collaborator

Trials

43

Recruited

6,600+

Citations

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

Efficacy and Safety of Actively Personalized Neoantigen ... Recently, neoantigen-based personalized vaccines have shown tremendous immunogenicity and safety in GBM. We aimed to systematically review the ...

2. nature.com nature.com/articles/s41467-024-51315-8

A real-world observation of patients with glioblastoma ... Our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05743595

NCT05743595 | Neoantigen-based Personalized DNA ... The personalized neoantigen DNA vaccine will be given once every 28 days for up to 6 doses. Retifanlimab is given at a fixed dose of 500 mg every 28 days.

4. scientificarchives.com scientificarchives.com/article/personalized-neoantigen-dna-cancer-vaccines-current-status-and-future-perspectives

Personalized Neoantigen DNA Cancer Vaccines In recent years several publications have substantiated that NeoAgs delivered as a DNA vaccine can induce anti-tumor immunity in mouse models of cancer.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0304383522004323

Neoantigen discovery and applications in glioblastoma Personalized neoantigen-pulsed DC vaccine therapy has long been considered as a promising strategy to attack tumor cells more effectively and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04015700

Neoantigen-based Personalized DNA Vaccine in Patients ... This is a single institution, open-label, single arm, study assessing the safety, feasibility, and immunogenicity of a personalized neoantigen-based vaccine in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02287428

NCT02287428 | Personalized NeoAntigen Cancer Vaccine ... This research study is studying a new type of vaccine as a possible treatment for patients with glioblastoma.