PEP-CMV Vaccine for Recurrent Brain Tumor

(PRiME Trial)

Overseen By Daniel Landi, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Eric Thompson, M.D.

Must not be taking: Immunosuppressants, Investigational drugs, Corticosteroids

Disqualifiers: Pregnancy, Active infection, Immunosuppressive disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 3

Duration: Initial phase: 6 weeks, then monthly for up to 10 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine called PEP-CMV to determine its safety for individuals with certain recurrent brain tumors, specifically medulloblastoma and malignant glioma. The vaccine targets the cytomegalovirus (CMV), which may play a role in these tumors. The trial seeks participants whose brain tumors have returned after initial treatment. Eligible participants have previously been diagnosed with medulloblastoma or high-grade glioma and have experienced a worsening condition despite earlier treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on certain immunosuppressive agents or high doses of corticosteroids. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that PEP-CMV is likely to be safe for humans?

Research has shown that the PEP-CMV vaccine is generally well-tolerated by patients with brain tumors who have undergone several treatments. One study found that patients receiving the PEP-CMV vaccine experienced an immune response with few serious side effects. This suggests the vaccine is generally safe for individuals with medulloblastoma or malignant glioma. Although this treatment remains in the early testing phase, with safety as a primary focus, the results so far are promising for potential trial participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for recurrent brain tumors, which often involve surgery, radiation, and chemotherapy, the PEP-CMV vaccine takes a novel approach by harnessing the immune system to target the tumor. This vaccine specifically trains the immune system to recognize and attack cells infected with cytomegalovirus (CMV), which is often found in brain tumor cells. Researchers are excited because this method could offer a more targeted treatment with potentially fewer side effects, and it opens up possibilities for using the body’s own defenses to fight the cancer.

What evidence suggests that the PEP-CMV vaccine might be an effective treatment for recurrent brain tumors?

Research has shown that the PEP-CMV vaccine, which participants in this trial will receive, may help treat recurring brain tumors like medulloblastoma and malignant glioma. One study found that the vaccine is generally safe and can activate a specific immune response in patients who have undergone many treatments. Among these patients, 26.6% were still alive 12 months after receiving the vaccine, which is significant given their advanced condition. The vaccine targets a protein from the cytomegalovirus, called pp65, which may help the immune system attack cancer cells. These early findings suggest that PEP-CMV could offer hope for patients with difficult-to-treat brain tumors. ^{1 2 5 6 7}

Who Is on the Research Team?

Daniel Landi, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for patients aged 3-35 with recurrent medulloblastoma or malignant glioma who've had prior treatment. They must have stable neurological deficits, if any, and meet specific blood count and organ function criteria. Pregnant individuals, those with active infections or other serious illnesses, or on high-dose steroids are excluded.

Inclusion Criteria

My kidney function, measured by creatinine, is within normal range.

I was previously diagnosed with a serious brain tumor.

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

Exclusion Criteria

I do not have any serious illnesses unrelated to my cancer.

I have active kidney, heart, or lung disease.

I am taking medication to suppress my immune system for another health issue.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive temozolomide and PEP-CMV vaccine. Temozolomide is administered for 5 days, and the PEP-CMV vaccine is given every 2 weeks for the first 3 doses, then monthly.

Initial phase: 6 weeks, then monthly for up to 10 years

3 visits (every 2 weeks), then monthly visits

Follow-up

Participants are monitored for safety and immune response effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• PEP-CMV

Trial Overview PEP-CMV vaccine is being tested for safety in this study. It's designed for patients whose pediatric brain tumors have come back after initial treatments. The vaccine includes a synthetic peptide aimed at stimulating the immune system to fight the tumor.

How Is the Trial Designed?

Group I: PEP-CMV Experimental Treatment 1 Intervention

Cytomegalovirus (CMV)-specific peptide vaccine (PEP-CMV)

Who Is Running the Clinical Trial?

Eric Thompson, M.D.

Lead Sponsor

Trials

2

Recruited

60+

Gary Archer Ph.D.

Lead Sponsor

Trials

12

Recruited

290+

Daniel Landi

Lead Sponsor

Trials

2

Recruited

30+

Pediatric Brain Tumor Foundation

Collaborator

Trials

2

Recruited

80+

Annias Immunotherapeutics, Inc.

Collaborator

Trials

2

Recruited

60+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2039

Outcomes and immune response after peptide vaccination ... PEP-CMV is well-tolerated and elicits an antigen-specific immune response in heavily pretreated, multiply recurrent patients with a 12-month OS of 26.6%.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03299309

PEP-CMV in Recurrent MEdulloblastoma/Malignant Glioma The primary goal of this prospective clinical trial is to evaluate the safety of PEP-CMV in patients with recurrent medulloblastoma and malignant glioma.

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-07366

A Peptide Vaccine (PEP-CMV) for the Treatment of ... This phase II trial studies how well a peptide vaccine (PEP-CMV) works in treating pediatric patients with newly diagnosed high-grade glioma (HGG) and ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40506525/

A peptide vaccine targeting the CMV antigen pp65 in ... This single-arm phase 1 trial ( NCT03299309 ) assessed the safety and immunogenicity of a peptide vaccine (PEP-CMV) targeting pp65 in individuals (3-35 years ...

5. reporter.nih.gov reporter.nih.gov/search/qT5Tz_iNV0Sb9T-9kRczFw/project-details/11029506

Phase 1/2 trial of PEP-CMV + nivolumab for newly diagnosed ... Results from a recently completed Phase I clinical trial (PRiME, NCT03299309) of 42 patients age 3-35 with recurrent HGG/DMG and MB demonstrated significant ...

6. trials.braintumor.org trials.braintumor.org/trials/NCT05096481

PEP-CMV Vaccine Targeting CMV Antigen to Treat Newly ... This study will address the question of whether targeting CMV antigens with PEP-CMV can serve as a novel immunotherapeutic approach in pediatric patients.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05096481

Study Details | NCT05096481 | PEP-CMV Vaccine ... This study will address the question of whether targeting CMV antigens with PEP-CMV can serve as a novel immunotherapeutic approach in pediatric patients.