Peptide Vaccine for Brain Cancer

(ETAPA I Trial)

Overseen By Mustafa Khasraw, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Immunosuppressive agents

Disqualifiers: Allergies, Brainstem tumor, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine, P30-EPS, designed to target specific proteins in aggressive brain tumors like glioblastoma. The goal is to determine if this vaccine can enhance the immune system's ability to fight cancer cells. This trial may suit individuals recently diagnosed with a specific type of brain tumor (grade IV glioma) who have undergone surgery but not yet received other treatments. Participants must meet certain health criteria and should not have other illnesses that could interfere with the study. 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 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.

Is there any evidence suggesting that the P30-EPS vaccine is likely to be safe for humans?

Research has shown that the P30-EPS vaccine, made from three small proteins mixed with Hiltonol®, has been safe in past studies. These studies found that patients tolerated the vaccine well, and it helped their immune systems fight cancer. Importantly, no serious side effects were reported, suggesting it is generally safe for people. As this is a new treatment for brain cancer, ongoing research will continue to provide more information about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for brain cancer, which often involve surgery, radiation, and chemotherapy, the P30-EPS vaccine is unique because it leverages the body's immune system to fight cancer. This vaccine includes three specific peptides—pp65, EphA2, and survivin—combined with Hiltonol®, which is designed to enhance the immune response. Researchers are excited about this approach because it targets tumor-associated antigens, potentially offering a more precise and less toxic alternative to conventional therapies. By activating the immune system to recognize and attack cancer cells, this treatment could provide new hope for better outcomes in brain cancer patients.

What evidence suggests that the P30-EPS vaccine might be an effective treatment for brain cancer?

Research has shown that the P30-EPS vaccine, which participants in this trial may receive, targets specific markers on brain cancer cells. These markers, known as tumor-associated antigens, include EphA2, CMV pp65, and survivin. By focusing on these antigens, the vaccine aims to trigger the body's immune system to attack the cancer cells. Early results suggest this method could help the immune system recognize and fight the tumor. While researchers are still collecting human data, the science behind this approach remains strong. ^{1 6 7 8 9}

Who Is on the Research Team?

Mustafa Khasraw, MBChB, MD, FRCP, FRACP

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• P30-EPS 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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

The SVX vaccine, which targets the tumor antigen survivin using long synthetic peptides, demonstrated strong immunogenicity and therapeutic efficacy in both healthy individuals and cancer patients, showing the potential to generate robust T-cell responses.

In murine tumor models, the SVX vaccine not only effectively eradicated tumors but also created long-lasting memory T-cell responses and improved the tumor microenvironment by increasing the infiltration of CD4+ and CD8+ T cells, suggesting a promising approach for cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Therapeutic Efficacy of a New Survivin LSP-Cancer Vaccine Containing CD4+ and CD8+ T-Cell Epitopes. Onodi, F., Maherzi-Mechalikh, C., Mougel, A., et al.[2020]

Citations

1. academic.oup.com academic.oup.com/neuro-oncology/article/27/Supplement_3/iii14/8272284

OS04.3.A P30-EPS PEPTIDE VACCINE IS SAFE AND ... The P30-EPS vaccine is a novel multi-epitope peptide immunotherapy targeting class I HLA-A2 epitopes of tumor-associated antigens (EphA2, CMV ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05283109

Study Details | NCT05283109 | ETAPA I: Peptide-based ... This is a phase 1b study of P30-linked EphA2, CMV pp65, and survivin vaccination (collectively called the P30-EPS vaccine) in HLA-A*0201 positive patients.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12418597/

Immunologic specificity in glioblastoma: Antigen discovery ... With standard therapy, median survival is around 20 months, emphasizing the need for novel therapies. Targeting tumor antigens (TAs), the ...

4. clinicaltrial.be clinicaltrial.be/en/details/17929?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Peptide-based Tumor Associated Antigen Vaccine i... Patients will receive seven P30 linked-EphA2, -CMV pp65, and -survivin (P30-EPS) peptide vaccines over two phases. The first 5 will be given ...

5. smartpatients.com smartpatients.com/trials/NCT05283109

Peptide-based Tumor Associated Antigen Vaccine in GBM This is a phase 1b study of P30-linked EphA2, CMV pp65, and survivin vaccination (collectively called the P30-EPS vaccine) in HLA-A*0201 ...

6. ctv.veeva.com ctv.veeva.com/study/etapa-i-peptide-based-tumor-associated-antigen-vaccine-in-gbm

Peptide-based Tumor Associated Antigen Vaccine in GBM This is a phase 1b study of P30-linked EphA2, CMV pp65, and survivin vaccination (collectively called the P30-EPS vaccine) in HLA-A\*0201 positive patients.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12166567/

Recent developments in peptide vaccines against ... These vaccines have been included in several clinical trials, demonstrating their safety and effectiveness by eliciting protective immune ...

8. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/p30-linked-epha2-cmv-pp65-survivin-peptide-vaccine-p30-eps

P30-linked EphA2/CMV pp65/survivin peptide vaccine ... Upon administration, P30-linked EphA2/CMV pp65/survivin peptide vaccine P30-EPS may elicit a cytotoxic T-lymphocyte (CTL) response against tumor cells ...

9. researchgate.net researchgate.net/publication/396184344_OS043A_P30-EPS_PEPTIDE_VACCINE_IS_SAFE_AND_IMMUNOGENIC_IN_NEWLY_DIAGNOSED_GLIOBLASTOMA_A_PHASE_1B_TRIAL

OS04.3.A P30-EPS PEPTIDE VACCINE IS SAFE AND ... CONCLUSION P30-EPS administered with Hiltonol demonstrated a favorable safety profile and elicited vaccine-specific immune responses in patients ...