P53MVA + Pembrolizumab for Ovarian Cancer

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Pregnancy, CNS metastases, Autoimmune, 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

Compensation: Varies

Number of Visits: 4

Duration: 49 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two treatments—a special vaccine (Modified Vaccinia Virus Ankara Vaccine Expressing p53) and a drug called pembrolizumab—in combating ovarian, primary peritoneal, or fallopian tube cancer that has returned after treatment. The vaccine boosts the body's immune response to target and destroy cancer cells, while pembrolizumab helps the immune system attack the cancer and may prevent its growth and spread. This trial may suit those whose ovarian cancer has returned within six months after completing their last round of platinum-based chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have received any non-oncology, viral vaccines within 30 days prior to starting the trial. It's best to discuss your current medications with the trial team to get specific guidance.

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

Research has shown that the p53MVA vaccine, when combined with pembrolizumab, is safe and may benefit certain patients. Studies indicate that patients tolerated this combination well, with no major safety issues. The p53MVA vaccine uses a virus to help the immune system identify and attack cancer cells. It has been widely studied for both infectious diseases and cancer treatment.

Pembrolizumab is already approved for other uses, so its safety profile is well-established. Studies on pembrolizumab for ovarian cancer found it was generally well-tolerated, with manageable side effects such as tiredness and nausea.

Overall, both treatments have been tested in people, and research supports their safety, making them promising options for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for ovarian cancer involve chemotherapy or surgery, but P53MVA + Pembrolizumab offers a new approach by combining immunotherapy with a targeted vaccine. Pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. The modified vaccinia virus Ankara vaccine expressing p53 is designed to stimulate an immune response specifically against cancer cells with p53 mutations, which are common in ovarian cancer. Researchers are excited because this combination has the potential to enhance the body's natural defenses, offering a more personalized and potentially more effective treatment option.

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

Research has shown that the p53MVA vaccine can help the immune system recognize and attack cancer cells. In this trial, participants will receive both the p53MVA vaccine and pembrolizumab. This combination has shown promise in treating ovarian cancer. Pembrolizumab, a treatment that boosts the immune system, has been proven to help patients with recurring ovarian cancer live longer. Early studies suggest that using both treatments together might help the body fight and shrink tumors more effectively than using either treatment alone. This combination has been found to be safe and may offer benefits for patients with certain types of cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Thanh Dellinger

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer who've had platinum-based chemotherapy within the last 6 months. They must have a specific p53 gene mutation or overexpression and be in good enough health to participate (ECOG <=2). Women of childbearing potential must agree to contraception guidelines.

Inclusion Criteria

I can care for myself and doctors expect me to live at least 3 more months.

I have had up to 4 chemotherapy treatments for my recurring cancer.

Meet specific laboratory criteria including ANC, platelets, hemoglobin, creatinine, bilirubin, AST, ALT, INR, aPTT, LVEF

Exclusion Criteria

I haven't had cancer treatment in the last 4 weeks.

I am currently being treated for an infection.

My family has a history of Li-Fraumeni syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab IV every 3 weeks and p53MVA SC every 3 weeks for up to 3 vaccines. Pembrolizumab cycles repeat every 3 weeks for up to 49 weeks.

49 weeks

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 24 months

1-3 weeks after treatment, then every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Modified Vaccinia Virus Ankara Vaccine Expressing p53
• Pembrolizumab

Trial Overview The study tests a combination of a modified vaccinia virus ankara vaccine expressing p53 (p53MVA) and pembrolizumab, an immunotherapy drug. The goal is to see if this combo can stimulate the immune system to fight cancer cells more effectively than current treatments.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab, p53MVA) Experimental Treatment 2 Interventions

Patients receive pembrolizumab IV over 30 minutes every 3 weeks and modified vaccinia virus ankara vaccine expressing p53 SC every 3 weeks for up to 3 vaccines. Cycles with pembrolizumab repeat every 3 weeks for up to 49 weeks 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

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02275039

p53MVA Vaccine and Gemcitabine Hydrochloride in ... Giving modified vaccinia virus ankara vaccine expressing p53 together with gemcitabine hydrochloride may work better in treating patients with ovarian ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2017-00555

P53MVA and Pembrolizumab in Treating Patients with ... This phase II trial studies how well modified vaccinia virus ankara vaccine expressing p53 (p53MVA) and pembrolizumab work in treating patients with ovarian ...

3. 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.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.e17040

A phase I study of a p53MVA vaccine in combination ... We previously reported that p53MVA was well tolerated at a dose of 5.6 x 108 pfu in patients (pts) with gastro-intestinal malignancies. GEM, a ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8802616/

Evaluation of safety and efficacy of p53MVA vaccine ... We have shown that the combination of p53MVA vaccine with pembrolizumab is feasible, safe, and may offer a clinical benefit in select group of patients.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02275039

p53MVA Vaccine and Gemcitabine Hydrochloride in ... Giving modified vaccinia virus ankara vaccine expressing p53 together with gemcitabine hydrochloride may work better in treating patients with ovarian ...

7. aacrjournals.org aacrjournals.org/cancerrescommun/article/3/12/2585/731759/Immunologic-Signatures-of-Peripheral-Blood-T-Cells

Immunologic Signatures of Peripheral Blood T Cells Reveal ... Our previous studies indicated that p53-reactive T cells were associated with clinical benefit in patients with advanced ovarian cancer who were treated ...

8. 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.