Peptide Vaccine for Brain Cancer

(ETAPA I Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Mustafa Khasraw, MBChB, MD, FRCP, FRACP

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Mustafa Khasraw, MBChB, MD, FRCP, FRACP

Must not be taking: Immunosuppressive agents

Disqualifiers: Allergies, Brainstem tumor, Heart failure, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new vaccine called P30-EPS in patients with a specific type of aggressive brain cancer. The vaccine helps the immune system recognize and attack cancer cells by using three special proteins.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions that co-medication that may interfere with study results, like immuno-suppressive agents, is not allowed. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the P30-EPS treatment for brain cancer?

Research on similar peptide vaccines, like those targeting survivin and EphA2, shows they can activate the immune system against brain cancer cells and have shown some promise in improving survival rates in patients with glioblastoma and other high-grade gliomas. ^{1 2 3 4 5}

Is the peptide vaccine for brain cancer safe for humans?

The peptide vaccine targeting glioma-associated antigens, including EphA2 and survivin, has been generally well tolerated in children with recurrent malignant gliomas, with no dose-limiting non-CNS (central nervous system) toxicity reported. ^{1 2 3 4 6}

What makes the P30-EPS vaccine treatment unique for brain cancer?

The P30-EPS vaccine is unique because it targets specific proteins (EphA2, CMV pp65, and survivin) that are overexpressed in brain cancer cells, aiming to stimulate the immune system to attack these cancer cells. This approach is different from traditional treatments like chemotherapy and radiation, as it focuses on harnessing the body's immune response to fight the cancer. ^{1 2 4 5 7}

Research Team

Mustafa Khasraw, MBChB, MD, FRCP, FRACP

Principal Investigator

Duke University

Eligibility Criteria

Adults over 18 with a specific type of brain tumor called WHO grade IV malignant glioma that hasn't been treated yet. They must have had surgery to remove the tumor, be HLA A*0201 positive, and not pregnant or breastfeeding. Participants need good blood counts and organ function, and agree to use effective contraception.

Inclusion Criteria

I am not pregnant or breastfeeding and use effective birth control.

I am a man who will use effective birth control during and for 6 months after the trial.

Hemoglobin ≥ 9.0 g/dl, absolute neutrophil count (ANC) ≥ 1,000 cells/µl, platelets ≥ 100,000 cells/µl.

Exclusion Criteria

I have an autoimmune disease, but it's not well-controlled hypothyroidism or diabetes.

I have not had specific surgeries or radiation treatments for a brain tumor.

I have only had surgery, steroids, or standard chemoradiation before joining.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Chemotherapy

Participants undergo standard of care surgical resection followed by 6 weeks of radiation therapy with concomitant temozolomide

6 weeks

Priming Phase

Participants receive the first 5 P30-EPS peptide vaccines

3 weeks

5 visits (in-person)

Booster Phase

Participants receive 2 additional P30-EPS peptide vaccines and Hiltonol® injections

8 weeks

2 visits (in-person), Hiltonol® injections administered at home every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Treatment Details

Interventions

• P30-EPS Vaccine (Cancer Vaccine)

Trial Overview The trial is testing a new vaccine made from peptides linked to proteins found in tumors (P30-EPS) for patients with a certain genetic makeup. It's an early-phase study to see if this vaccine can help treat brain tumors without previous treatment.

Participant Groups

Group I: Tumor Associated Antigen Peptide Vaccine in Combination with Hiltonol Experimental Treatment 2 Interventions

The study vaccine is comprised of three different peptides (small proteins) mixed with Hiltonol®. The three peptides that make up the study vaccine are called pp65, EphA2, and survivin.

Who Is Running the Clinical Trial?

Mustafa Khasraw, MBChB, MD, FRCP, FRACP

Lead Sponsor

Trials

4

Recruited

120+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

In a Phase 2 study involving patients with recurrent glioblastoma, the multi-epitope long peptide vaccine TAS0313 showed an objective response rate of 11.1% and a disease control rate of 44.4%, indicating some efficacy in this challenging cancer.

TAS0313 was found to have an acceptable safety profile, with common side effects including injection site reactions and fever, but no severe adverse events or deaths reported during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy and safety of TAS0313 in adults with recurrent glioblastoma. Narita, Y., Okita, Y., Arakawa, Y.[2022]

A pilot trial involving 12 children with recurrent high-grade gliomas showed that peptide vaccinations targeting glioma-associated antigens were generally well tolerated, with no significant non-CNS toxicity reported.

The treatment demonstrated preliminary immunological responses in 9 out of 10 children tested, with one child experiencing a partial response lasting over 2 years, suggesting potential clinical activity despite the overall poor prognosis of these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigen-specific immunoreactivity and clinical outcome following vaccination with glioma-associated antigen peptides in children with recurrent high-grade gliomas: results of a pilot study. Pollack, IF., Jakacki, RI., Butterfield, LH., et al.[2021]

The INTERCEPT H3 trial is investigating the safety and immunogenicity of the H3K27M-vac vaccine in combination with standard radiotherapy and the immune checkpoint inhibitor atezolizumab in 15 adult patients with newly diagnosed diffuse midline gliomas (DMG) carrying the H3K27M mutation.

Preliminary results from earlier studies suggest that the H3K27M-vac vaccine can induce specific immune responses that may help suppress tumor growth, making it a promising treatment strategy for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

INTERCEPT H3: a multicenter phase I peptide vaccine trial for the treatment of H3-mutated diffuse midline gliomas. Grassl, N., Sahm, K., Süße, H., et al.[2023]

SurVaxM, a peptide vaccine targeting the survivin protein in glioblastoma cells, was found to be safe and well tolerated in a phase IIa trial with 64 patients, showing no serious adverse events related to the vaccine.

The combination of SurVaxM with adjuvant temozolomide (TMZ) resulted in a high progression-free survival rate of 95.2% at 6 months and a median overall survival of 25.9 months, indicating promising efficacy in treating newly diagnosed glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IIa Study of SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma. Ahluwalia, MS., Reardon, DA., Abad, AP., et al.[2023]

Immunotherapy, particularly using active specific vaccination like the survivin-targeted peptide vaccine (SurVaxM), shows promise as a potential adjunctive treatment for malignant gliomas, especially given the limitations of conventional therapies.

Despite the optimism surrounding immunotherapy for gliomas, significant challenges remain in translating laboratory findings into effective Phase I and II clinical trials, highlighting the complexity of developing these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges in the development of a survivin vaccine (SurVaxM) for malignant glioma. Fenstermaker, RA., Ciesielski, MJ.[2022]

EphA2 is overexpressed in glioblastoma multiforme and anaplastic astrocytoma, making it a potential target for glioma vaccine strategies, as it is less expressed in normal brain tissues.

The study demonstrated that a synthetic peptide (EphA2883-891) can stimulate a strong immune response in both human immune cells and in HLA-A2 transgenic mice, indicating its potential as an effective antigen for targeted glioma vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EphA2 as a glioma-associated antigen: a novel target for glioma vaccines. Hatano, M., Eguchi, J., Tatsumi, T., et al.[2020]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy and safety of TAS0313 in adults with recurrent glioblastoma. [2022]

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

Antigen-specific immunoreactivity and clinical outcome following vaccination with glioma-associated antigen peptides in children with recurrent high-grade gliomas: results of a pilot study. [2021]

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

INTERCEPT H3: a multicenter phase I peptide vaccine trial for the treatment of H3-mutated diffuse midline gliomas. [2023]

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

Phase IIa Study of SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Challenges in the development of a survivin vaccine (SurVaxM) for malignant glioma. [2022]

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

EphA2 as a glioma-associated antigen: a novel target for glioma vaccines. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

High Therapeutic Efficacy of a New Survivin LSP-Cancer Vaccine Containing CD4+ and CD8+ T-Cell Epitopes. [2020]