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

Trial Summary

What is the purpose of this trial?

This phase I/II trial tests the safety, side effects, best dose, and effectiveness of multi-epitope folate receptor alpha-loaded dendritic cell vaccine (FRalphaDC) with pembrolizumab in treating patients with ovarian, fallopian tube, or primary peritoneal cancer (collectively known as ovarian cancer) that that has come back (after a period of improvement) (recurrent). Ovarian cancer is the most lethal gynecologic malignancy in the United States. While the majority of patients achieve a remission from ovarian cancer with the combination of aggressive cytoreductive surgery and cytotoxic chemotherapy, over 80% of patients develop recurrence within 3 years of completion of treatment. Additional treatments are needed for recurrence, but the standard treatment modalities are non-curative in nature due to the development of drug resistance. As such, there is a great unmet need for treatment strategies that utilize new mechanisms to which drug resistance does not develop. FRalphaDC is a dendritic cell vaccine that is made from the white blood cells collected from a procedure call apheresis. The white blood cells are treated to make dendritic cells, which will then be incubated with peptides, which are pieces of a protein known as "folate receptor alpha" (FRalpha), a protein that is found in high levels on ovarian cancer cells. Dendritic cell vaccines work by boosting the immune system (a system in the body that protect against infection) to recognize and destroy the tumor cells by targeting the FRalpha protein. 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 FRalphaDC vaccine with pembrolizumab may be a safe and effective treatment for recurrent ovarian cancer.

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.

What data supports the effectiveness of the treatment Dendritic Cell Vaccine + Pembrolizumab for Ovarian Cancer?

Research shows that a similar dendritic cell vaccine targeting folate receptor alpha (FRα) in ovarian cancer patients is safe and can lead to prolonged remission by inducing specific immune responses. Additionally, pembrolizumab has been studied for its safety and antitumor activity in ovarian cancer, suggesting potential benefits when combined with other therapies. ^{1 2 3 4 5}

Is the Dendritic Cell Vaccine + Pembrolizumab treatment safe for humans?

The Dendritic Cell Vaccine targeting folate receptor alpha has been shown to be safe in a small study with ovarian cancer patients, with no severe side effects reported. Pembrolizumab, used in various studies for ovarian cancer, has been evaluated for safety, but specific safety details are not provided in the abstracts. ^{1 2 3 5 6}

What makes the dendritic cell vaccine and pembrolizumab treatment unique for ovarian cancer?

This treatment is unique because it combines a dendritic cell vaccine that targets the folate receptor alpha, which is overexpressed in ovarian cancer, with pembrolizumab, an immune checkpoint inhibitor. The vaccine is designed to boost the body's immune response specifically against ovarian cancer cells, potentially leading to prolonged remission. ^{1 2 3 5 7}

Research Team

Matthew S. Block, MD, PhD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

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

I am 18 years old or older.

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Th17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients. [2020]

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

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022]

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

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

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

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials. [2023]

5. England 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. [2021]

6. England 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. [2022]

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

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