VRP-HER2 Vaccine + Pembrolizumab for Breast Cancer

Overseen By Amy Hobeika

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Herbert Lyerly

Must be taking: Trastuzumab, Pertuzumab

Must not be taking: Cytotoxic chemotherapy, Anti-estrogen therapy

Disqualifiers: CNS metastases, Active infection, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 15 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating breast cancer using a vaccine called VRP-HER2, either alone or with pembrolizumab, an immunotherapy drug. Researchers aim to assess how these treatments impact the cancer and the immune system. Participants will join one of three groups: one receiving the vaccine, another receiving pembrolizumab, and the last receiving both. This trial suits individuals previously treated with trastuzumab and pertuzumab for breast cancer who are experiencing manageable side effects. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking certain medications, such as cytotoxic chemotherapy, anti-estrogen therapy, targeted small molecule therapy, or radiation therapy, at least 3 weeks before starting the trial. Additionally, you should not be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the VRP-HER2 vaccine is generally safe and well-tolerated when used alone. Studies have found no harmful effects at any dose, indicating its safety for people.

Pembrolizumab, already approved by the FDA for other uses, has more extensive safety data. While it can cause side effects, some of which may be serious, it is generally safe and effective when used correctly.

Research continues on using both treatments together. Although detailed safety data on the combination is not yet available, the safety records of each treatment are encouraging. Participants in current studies appear to handle the combination well, but more information is needed to confirm this. It is important to discuss potential risks with healthcare providers before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the VRP-HER2 Vaccine + Pembrolizumab treatment for breast cancer because it offers a novel approach by combining a cancer vaccine with immunotherapy. Unlike traditional treatments like chemotherapy, which directly attack cancer cells, the VRP-HER2 Vaccine trains the immune system to recognize and target HER2-positive cancer cells. When paired with Pembrolizumab, an immune checkpoint inhibitor, this combination enhances the body's ability to fight cancer by blocking proteins that prevent immune cells from attacking tumors. This dual approach not only aims to improve the immune response but also holds the potential for more durable and effective cancer control.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Studies have shown that the VRP-HER2 vaccine can boost certain immune cells targeting HER2, potentially aiding in the fight against HER2-positive breast cancer. Research indicates that pembrolizumab, an immunotherapy drug, can extend the lives of some breast cancer patients when combined with traditional treatments. In this trial, participants will receive either the VRP-HER2 vaccine alone, pembrolizumab alone, or a combination of both. Early findings suggest that combining the VRP-HER2 vaccine with pembrolizumab might be more effective than using the vaccine alone. This combination could enhance the body's immune response against cancer cells. Based on these findings, the combination shows promise for treating HER2-positive breast cancer. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

Adults over 18 with breast cancer, who've had prior treatment with trastuzumab and pertuzumab, can join this trial. They must have a tumor biopsy available, resolved side effects from previous treatments to mild levels, normal heart function, and be able to use contraception. Exclusions include active brain metastases, certain infections or conditions that could affect the study's outcome or patient safety.

Inclusion Criteria

All side effects from my previous cancer treatments are mild, except for possible hair loss, nerve pain, and tiredness.

Be willing and able to provide written informed consent/assent for the trial.

Ability to return to Duke University Medical Center for adequate follow-up as required by this protocol.

Exclusion Criteria

You are allergic to pembrolizumab or any of the substances it contains.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

I have had pneumonitis treated with steroids or currently have it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VRP-HER2 immunizations and/or pembrolizumab based on randomization into one of three arms

15 weeks

Injections every 2 weeks and infusions every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• VRP-HER2

Trial Overview This phase II trial tests VRP-HER2 vaccinations combined with pembrolizumab in patients with breast cancer. Initially there's a Safety Arm; if safe, participants are randomized into three groups: one receiving just the vaccine (Arm A), another getting only pembrolizumab (Arm B), and the third both treatments (Arm C).

How Is the Trial Designed?

Group I: VRP-HER2 Vaccine + Pembrolizumab Experimental Treatment 2 Interventions

VRP-HER2 Vaccine 4 x 10EE8 IU given as a single injection every 2 weeks for 3 injections total (Cycle 1: Day 1 and Day 15 Cycle 2: Day 8)+ 5 administrations of Pembrolizumab 200 mg every 3 weeks for 5 total IV infusions (Day 1 of each 3 week cycle x 5 cycles)

Group II: VRP-HER2 Vaccine Active Control 1 Intervention

VRP-HER2 Vaccine 4 x 10EE8 IU given as a single injection every 2 weeks for 3 injections total (Cycle 1: Day 1 and Day 15 Cycle 2: Day 8)

Group III: Pembrolizumab Active Control 1 Intervention

5 administrations of Pembrolizumab 200 mg every 3 weeks for 5 total IV infusions (Day 1 of each 3 week cycle x 5 cycles)

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Herbert Lyerly

Lead Sponsor

Trials

5

Recruited

60+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

The AE37 vaccine, which targets the HER-2/neu protein in breast cancer, has been shown to be safe and effective in generating long-lasting immune responses in patients, regardless of their HER-2/neu expression levels.

Early clinical trials indicate that the AE37 vaccine may help prevent breast cancer recurrence, highlighting its potential as a promising immunotherapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AE37: a novel T-cell-eliciting vaccine for breast cancer. Sears, AK., Perez, SA., Clifton, GT., et al.[2014]

In a study of 186 breast cancer patients, those vaccinated with the E75 + GM-CSF vaccine showed a lower recurrence rate (8.3%) compared to the control group (14.8%), although this difference was not statistically significant (P = 0.17).

Vaccinated patients who did experience recurrences had more aggressive disease characteristics, such as higher tumor grades and nodal stages, but they exhibited similar immune responses to the vaccine as those who did not recur, suggesting that the vaccine may still provide some protective benefits against more aggressive forms of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of immunologic response and recurrence patterns among patients with clinical recurrence after vaccination with a preventive HER2/neu peptide vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Amin, A., Benavides, LC., Holmes, JP., et al.[2020]

The E75 vaccine demonstrated significant effectiveness in improving immune responses and clinical outcomes, such as reduced recurrence rates and increased disease-free survival in breast cancer patients, with minimal side effects reported.

The GP2 vaccine also showed promise in eliciting immune responses, particularly in increasing CD8+ T-cell numbers, but further clinical trials are necessary to establish its efficacy compared to the E75 vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of HER2 peptide vaccines in patients with breast cancer: a systematic review and meta-analysis. You, Z., Zhou, W., Weng, J., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In patients with hormone receptor-positive metastatic breast cancer, higher levels of specific immune cells (effector memory CD8+ and CD4+ T cells) before treatment were associated with better responses to the combination therapy of palbociclib, pembrolizumab, and letrozole, compared to those receiving only pembrolizumab and letrozole.

The combination therapy also led to significant changes in myeloid cell composition, including increased mature dendritic cells and decreased classical monocytes, which may enhance the immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer. Egelston, C., Guo, W., Yost, S., et al.[2021]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

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