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

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies how well modified vaccinia virus ankara vaccine expressing p53 (p53MVA) and pembrolizumab work in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back (recurrent). Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving p53MVA and pembrolizumab together may work better in treating patients with ovarian, primary peritoneal, or fallopian tube cancer.

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 the combination of p53MVA vaccine and pembrolizumab safe for humans?

The combination of the p53MVA vaccine and pembrolizumab has been evaluated in patients with advanced solid tumors, including ovarian cancer, and has shown to activate immune cells without immediate clinical benefit. Safety data from these studies suggest that the treatment is generally safe, but specific side effects or adverse reactions were not detailed in the provided abstracts. ^{1 2 3 4 5}

What makes the P53MVA + Pembrolizumab treatment unique for ovarian cancer?

This treatment combines a vaccine (p53MVA) that targets a specific protein (p53) often found in cancer cells with pembrolizumab, a drug that helps the immune system attack cancer by blocking a protein (PD-1) that prevents immune cells from killing cancer cells. This combination aims to enhance the immune response against ovarian cancer, offering a novel approach compared to traditional chemotherapy. ^{1 2 3 6 7}

What data supports the effectiveness of the treatment P53MVA + Pembrolizumab for ovarian cancer?

Research suggests that the combination of the p53MVA vaccine and pembrolizumab may enhance the immune response in patients with advanced ovarian cancer, as p53-reactive T cells were linked to clinical benefits in previous studies. However, the combination's effectiveness in providing clinical benefits requires further investigation, as initial studies showed immune activation but not immediate clinical improvement. ^{1 2 3 6 7}

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

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]

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]

Citations

1. 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]

2. Italy pubmed.ncbi.nlm.nih.gov

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

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

p53-Reactive T Cells Are Associated with Clinical Benefit in Patients with Platinum-Resistant Epithelial Ovarian Cancer After Treatment with a p53 Vaccine and Gemcitabine Chemotherapy. [2022]

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

Overcoming immunosuppression to enhance a p53MVA vaccine. [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

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Antigen-specific immunotherapy in ovarian cancer and p53 as tumor antigen. [2019]