Vaccine + Pembrolizumab for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Investigational agents, Corticosteroids

Disqualifiers: Pregnancy, Brain metastasis, Autoimmune disease, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 7

Duration: 19 weeks

11 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies a combination of a special vaccine and pembrolizumab to treat patients with advanced solid tumors that haven't responded to other treatments. The vaccine helps the immune system recognize and attack cancer cells, while pembrolizumab boosts the immune system's ability to fight the cancer. Pembrolizumab has shown effectiveness in patients who have already received other treatments, with better outcomes and fewer side effects compared to some standard treatments.

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 use systemic corticosteroids (medications that reduce inflammation) while participating. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment combining the p53MVA vaccine and pembrolizumab for cancer?

In a study, a patient with triple negative breast cancer experienced complete regression of skin metastases after receiving the p53MVA vaccine with pembrolizumab, showing a strong immune response and lasting clinical benefit for 6 months. ^{1 2 3 4 5}

Is the combination of p53MVA vaccine and pembrolizumab safe for humans?

The combination of the p53MVA vaccine and pembrolizumab has been studied in patients with advanced cancers, and while it has shown some promising immune responses, the safety data specifically for this combination is limited. Pembrolizumab alone has been used safely in various cancers, but the specific safety profile of the combination with the p53MVA vaccine needs more research. ^{1 2 4 6 7}

How is the Vaccine + Pembrolizumab treatment different from other cancer treatments?

This treatment combines a vaccine that targets a specific protein (p53) with pembrolizumab, an immune checkpoint inhibitor, to enhance the body's immune response against cancer. Unlike traditional chemotherapy, this approach aims to boost the immune system's ability to fight cancer cells by activating specific T cells and blocking proteins that prevent the immune system from attacking tumors. ^{1 2 3 4 5}

Research Team

Vincent Chung

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with advanced solid tumors that can't be removed by surgery or have spread and didn't respond to previous treatments. Participants must understand the study, sign consent, have certain blood counts and organ function levels, use contraception if needed, and not be pregnant. They should also not have severe allergies to egg proteins or a history of certain immune reactions.

Inclusion Criteria

All subjects must have the ability to understand and the willingness to sign an Institutional Review Board (IRB) approved consent form

You must have enough neutrophils in your blood, at least 1,500 per microliter.

Women of child-bearing potential must use contraception prior to study entry and for six months after study participation; sexually active men whose partners are women of childbearing age must use condoms

Exclusion Criteria

Radiotherapy within 4 weeks prior to entering the study is an exclusion criterion

Non-compliance with the safety monitoring requirements of the study will result in exclusion

Patients receiving any additional investigational agents or radiation therapy are excluded

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab IV and p53MVA vaccine SC in weeks 1, 4, and 7, with potential additional doses in weeks 10, 13, 16, and 19

19 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 19 weeks

Treatment Details

Interventions

• Modified Vaccinia Virus Ankara Vaccine Expressing p53
• Pembrolizumab

Trial Overview The trial tests a vaccine therapy using a modified virus expressing p53 combined with pembrolizumab (a monoclonal antibody) against various solid tumors. The goal is to see if this combination helps the immune system destroy cancer cells more effectively than current treatments.

Participant Groups

Group I: Treatment (p53MVA, pembrolizumab) Experimental Treatment 3 Interventions

Patients receive pembrolizumab IV over 30 minutes followed by modified vaccinia virus Ankara vaccine expressing p53 SC at least 30 minutes later once in weeks 1, 4, and 7. Patients may receive additional doses of pembrolizumab in weeks 10, 13, 16, and 19, for a maximum of 7 doses if there are no signs of progressive disease. Treatment continues in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The Phase I trial of the p53-targeting modified vaccinia Ankara (p53MVA) vaccine showed that it can enhance T-cell recognition of the p53 protein in patients with refractory gastrointestinal cancers.

However, the T-cell response was temporary, indicating that combining p53MVA with immunomodulatory agents may be necessary to achieve lasting clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming immunosuppression to enhance a p53MVA vaccine. Hardwick, N., Chung, V., Cristea, M., 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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Evaluation of safety and efficacy of p53MVA vaccine combined with pembrolizumab in patients with advanced solid cancers. [2022]

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

Immunologic Signatures of Peripheral Blood T Cells Reveal the Outcome of p53MVA Vaccine and Pembrolizumab Treatment in Patients with Advanced Ovarian Cancer. [2023]

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

Overcoming immunosuppression to enhance a p53MVA vaccine. [2021]

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

Complete regression of cutaneous metastases with systemic immune response in a patient with triple negative breast cancer receiving p53MVA vaccine with pembrolizumab. [2021]

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

p53MVA therapy in patients with refractory gastrointestinal malignancies elevates p53-specific CD8+ T-cell responses. [2021]

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

Safety and immunogenicity of modified vaccinia Ankara (ACAM3000): effect of dose and route of administration. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]