Dendritic Cell Vaccine + Pembrolizumab for Ovarian Cancer

(FRAPPE Trial)

Recruiting at 2 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Mayo Clinic

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

Disqualifiers: Pregnancy, HIV, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 91

Duration: Up to 22 cycles

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for ovarian cancer that has returned after prior treatment. It combines a dendritic cell vaccine (Multi-epitope Folate Receptor Alpha-loaded Dendritic Cell Vaccine), which helps the immune system recognize and attack cancer cells, with pembrolizumab, a medication that boosts the immune system's ability to fight cancer. The goal is to assess the safety and effectiveness of this combination for patients whose cancer has recurred. This trial may suit those with ovarian, fallopian tube, or primary peritoneal cancer that has returned after platinum-based chemotherapy. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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

The trial requires a 'washout' period (time without taking certain medications) of at least 5 weeks between the last anti-cancer treatment and the start of the trial therapy. This means you may need to stop certain medications before joining the trial.

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

Research shows that pembrolizumab, one of the treatments in this trial, has been tested in other ovarian cancer studies. These studies found that pembrolizumab is usually well-tolerated. Common side effects include tiredness, nausea, and itching, while serious side effects are less common. Previous studies have examined the safety and tolerability of the multi-epitope folate receptor alpha-loaded dendritic cell vaccine (FRalphaDC). These studies suggest that the vaccine is generally well-tolerated, with some patients experiencing mild side effects like injection site reactions or a mild fever. Since both treatments are still in the early to middle stages of testing together, researchers are closely monitoring them to understand all side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the dendritic cell vaccine combined with pembrolizumab for ovarian cancer because it offers a novel approach compared to standard treatments like surgery, chemotherapy, and targeted therapies. Unlike traditional methods, this treatment leverages the body's immune system by using a dendritic cell vaccine loaded with folate receptor alpha, a protein commonly found on ovarian cancer cells, to precisely target and attack the cancer. Additionally, pembrolizumab, an immunotherapy drug, helps boost the immune response by blocking the PD-1 pathway, which tumors often exploit to evade immune detection. This combination could potentially improve the effectiveness of the treatment and offer a new hope for patients with ovarian cancer.

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

Research has shown promising results for both treatments tested in this trial. The folate receptor alpha-loaded dendritic cell vaccine (FRalphaDC), which participants will receive, demonstrated potential in earlier studies. Specifically, five patients in those studies had complete responses, with their cancer halting progression for nearly seven months on average. This suggests the vaccine might enhance the immune system's ability to recognize and attack cancer cells.

Pembrolizumab, the other treatment in this trial, has already proven effective in treating various cancers. It has benefited patients with recurring ovarian cancer, with some experiencing disease stabilization. Participants will receive both FRalphaDC and Pembrolizumab, and combining these treatments could strengthen the immune response against ovarian cancer, offering hope for those with recurring cases. ^{1 2 4 6 7}

Who Is on the Research Team?

Matthew S. Block, MD, PhD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for adults with certain types of advanced ovarian, fallopian tube, or primary peritoneal cancer that has come back. Participants must be in good physical condition (ECOG PS 0 or 1), not pregnant, willing to use contraception if they can have children, and able to provide tissue samples. They should not have had prior anti-PD-1/L1 therapy for ovarian cancer or recent anticancer treatment and must not have other serious illnesses.

Inclusion Criteria

My blood, kidney, liver, and clotting tests are normal.

I am willing to have a central line placed if needed.

I am willing to give a sample of my previous biopsy for research.

Exclusion Criteria

I do not have any severe illnesses besides my current condition.

I have another cancer that hasn't needed serious treatment in the last 3 years.

Pregnant persons

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and Vaccine Manufacturing

Patients undergo apheresis for multi-epitope folate receptor alpha-loaded dendritic cell vaccine manufacturing

1 week

Treatment

Patients receive FRalphaDC vaccine intradermally and pembrolizumab intravenously. Cycles repeat every 21 days for up to 8 cycles, then every 42 days for up to cycle 22

Up to 22 cycles

Intradermal and intravenous administration on day 1 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Follow-up at 90 days after last dose, every 3 months until 24 months, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Multi-epitope Folate Receptor Alpha-loaded Dendritic Cell Vaccine
• Pembrolizumab

Trial Overview The study tests a vaccine made from the patient's own white blood cells treated with peptides (FRaDCs) combined with pembrolizumab, an immunotherapy drug. The goal is to see if this combo helps the immune system destroy tumor cells in patients with recurrent cancers mentioned above.

How Is the Trial Designed?

Group I: Treatment (apheresis, FRalphaDC, pembrolizumab) Experimental Treatment 7 Interventions

Patients undergo apheresis for multi-epitope folate receptor alpha-loaded dendritic cell vaccine manufacturing on study. Patients then receive multi-epitope folate receptor alpha-loaded dendritic cell vaccine ID on day 1 of cycles 1-5 and pembrolizumab IV over 30 minutes on day 1 of cycles 1-8. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patient then receive multi-epitope folate receptor alpha-loaded dendritic cell vaccine ID on day 1 of odd cycles and pembrolizumab IV over 30 minutes on day 1 of remaining cycles. Cycles repeat every 42 days for up to cycle 22 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI as well as blood sample collection throughout the trial. Patients undergo biopsy on study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

NanoPass Technologies Ltd

Industry Sponsor

Trials

8

Recruited

1,800+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 44 women with recurrent ovarian cancer treated with immune checkpoint inhibitors, the overall response rate was 14.2%, with a notable correlation between platinum sensitivity and response in high-grade serous ovarian cancer (HGSOC) patients.

Severe immune-related adverse events (irAEs) occurred in 47.7% of patients, with elevated hepatic or pancreatic enzymes being the most common, and a higher number of gene mutations appeared to protect against these specific adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials. Hinchcliff, E., Hong, D., Le, H., et al.[2023]

The combination of the FRα vaccine TPIV200 and the PD-L1 inhibitor durvalumab was well tolerated in 27 patients with advanced platinum-resistant ovarian cancer, showing a low grade 3 toxicity rate of 18.5%.

While the overall response rate was low (3.7% partial response and 33.3% stable disease), the median overall survival was notably long at 21 months, suggesting potential benefits from this immunotherapy approach in a heavily pretreated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: a phase II trial. Zamarin, D., Walderich, S., Holland, A., 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]

The study developed a method to create synthetic oligopeptides from unique ovarian cancer biomarkers, which could lead to highly specific immune responses against ovarian cancer.

These oligopeptides are designed to be non-crossreactive, potentially enhancing their effectiveness for immunodiagnostics, immunoprevention, and immunotherapy in ovarian cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oligopeptides for Immunotherapy Approaches in Ovarian Cancer Treatment. Kanduc, D.[2020]

The phase I clinical trial involving 19 ovarian cancer patients demonstrated that a vaccine using Th17-inducing dendritic cells is safe, with no severe adverse events reported, and successfully induces immune responses against the folate receptor alpha (FRα).

Of the 18 patients evaluated for efficacy, 39% remained recurrence-free after a median follow-up of 49.2 months, suggesting that the vaccine may contribute to prolonged remission in ovarian cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Th17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients. Block, MS., Dietz, AB., Gustafson, MP., et al.[2020]

In a study involving patients with recurrent platinum-resistant ovarian cancer, the combination of pembrolizumab, cisplatin, and gemcitabine resulted in an overall response rate of 60%, but the duration of response was relatively short at 4.9 months.

The addition of pembrolizumab did not show a significant benefit over chemotherapy alone, leading to the decision to close the trial for further accrual after an interim analysis indicated modest outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. Walsh, CS., Kamrava, M., Rogatko, A., et al.[2022]

The combination of pembrolizumab and carboplatin was found to be well-tolerated and showed activity in patients with recurrent platinum-resistant ovarian cancer, with a median overall survival of 11.3 months.

Patients with a higher ratio of peripheral CD8+PD1+Ki67+ T cells to tumor burden had significantly longer overall survival, suggesting this ratio could help identify those who may benefit more from this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. Liao, JB., Gwin, WR., Urban, RR., et al.[2022]

Citations

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NCT06639074 | Folate Receptor Alpha Dendritic Cells ... This phase II trial compares the effect of folate receptor alpha dendritic cells (FRαDCs) to placebo in treating patients with stage III or IV ovarian, ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-03999

FRalphaDC Vaccine with Pembrolizumab for the Treatment ... This phase I/II trial tests the safety, side effects, best dose, and effectiveness of multi-epitope folate receptor alpha-loaded dendritic cell vaccine ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11154542/

Folate Receptor Alpha—A Novel Approach to Cancer Therapy This study found that five patients achieved complete response (CR), with a median response duration of 6.9 months (95% CI: 5.6–9.7) and an ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05920798?term=AREA%5BConditionSearch%5D(fallopian%20tube)%20AND%20AREA%5BBasicSearch%5D(dendritic%20vaccine)&rank=5

NCT05920798 | Vaccine Therapy Plus Pembrolizumab in ... This phase I/II trial tests the safety, side effects, best dose, and effectiveness of multi-epitope folate receptor alpha-loaded dendritic cell vaccine ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7560895/

Th17-inducing autologous dendritic cell vaccination promotes ... Folate receptor alpha peptide vaccine generates immunity in breast and ovarian cancer patients. Clin. Cancer Res. 2018;24:3014–3025. doi ...

6. clinicaltrial.be clinicaltrial.be/en/details/11906?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Vaccine Therapy for Patients With Stage IIIC-IV Ovarian E... I. Determine the safety and tolerability of folate receptor alpha dendritic cell (FRalphaDC) vaccination (folate receptor alpha-peptide loaded ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02111941

Vaccine Therapy for Patients With Stage IIIC-IV Ovarian ... This pilot clinical trial studies the safety and immunogenicity of vaccine therapy in treating patients with stage IIIC-IV ovarian epithelial, ...