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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores using a vaccine (Modified Vaccinia Virus Ankara Vaccine Expressing p53) and pembrolizumab to treat individuals with advanced solid tumors that have spread and cannot be surgically removed. The vaccine aims to boost the body’s immune system to fight cancer cells, while pembrolizumab works to halt tumor growth. It targets patients whose cancer has not responded to other treatments and who have specific types of cancer, such as lung or breast cancer, with certain genetic markers like a p53 mutation. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new therapy.

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.

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

A previous study found the Modified Vaccinia Virus Ankara (MVA) vaccine with p53 to be safe, with most side effects being mild and not very bothersome.

Research has shown that pembrolizumab is generally safe as well. In various trials, many participants experienced side effects, but these were usually mild. However, about 16% of patients had more serious side effects.

Overall, both treatments have undergone testing, and side effects are usually mild for most people. However, there remains a chance of more serious reactions, particularly with pembrolizumab. Discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment because it combines a novel vaccine with an established immunotherapy drug, pembrolizumab, to target cancer cells in a new way. Most cancer treatments focus on killing cancer cells directly, but this method uses a modified vaccinia virus Ankara vaccine to express p53, a protein often mutated in cancer cells, to boost the immune system's response against them. This combined approach could potentially enhance the effectiveness of pembrolizumab, which is already known for its ability to unleash the immune system against cancer cells. By targeting cancer with a personalized immune boost, this treatment aims to increase the chances of halting disease progression with potentially fewer side effects.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that the modified vaccinia virus Ankara (MVA) vaccine with p53 can help the body build an immune response to attack cancer cells. Studies have found that this vaccine increases the number of specific immune cells targeting tumors. In this trial, participants will receive both the MVA vaccine and pembrolizumab. Pembrolizumab, a type of targeted therapy, has demonstrated long-term effectiveness in treating various cancers, with some patients achieving a five-year survival rate of up to 22%. Together, these treatments aim to enhance the body's ability to fight cancer, especially when other therapies have not succeeded. ^{1 2 3 6 7}

Who Is on the Research Team?

Vincent Chung

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3260009/

Recombinant Modified Vaccinia Virus Ankara (MVA) ... The present study aims to understand the potential of MVAp53 vaccine to induce expansion of p53-specific cytotoxic T lymphocyte ex vivo in cancer patients.

2. reporter.nih.gov reporter.nih.gov/project-details/7055284

clinical evaluation of a poxvirus vaccine targeting p53 Recombinant modified vaccinia virus ankara (MVA) expressing wild-type human p53 induces specific antitumor CTL expansion.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X96001958

Highly attenuated modified vaccinia virus Ankara (MVA) as ... CL25 tumor established 3 days earlier. Most importantly, i.v. inoculation with MVA-LZ resulted in significantly prolonged survival of mice bearing three day old ...

4. ascopubs.org ascopubs.org/doi/10.1200/jco.2013.31.15_suppl.3089

A phase I study of an MVA vaccine targeting p53 in cancer. Conclusions: Our MVA p53 vaccine is well tolerated with minimal grade 1-2 toxicities. The highest dose tested is 5.6 x 108 pfu and additional ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01191684

Vaccine Therapy in Treating Patients With Colorectal, ... RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1937644823000655

Armored modified vaccinia Ankara in cancer immunotherapy MVA is a highly attenuated strain of vaccinia virus that has been extensively investigated as a vaccine vector for infectious diseases and cancer therapy.

7. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/modified-vaccinia-virus-ankara-vaccine-expressing-p53

modified vaccinia virus ankara vaccine expressing p53 Upon subcutaneous vaccination with MVA vaccine expressing p53, the expressed p53 may stimulate the host immune system to mount a p53-specific cytotoxic T- ...