Dendritic Cell Vaccine + Pembrolizumab for Ovarian Cancer

(FRAPPE Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Matthew S. Block, MD, PhD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Mayo Clinic

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

Disqualifiers: Pregnancy, HIV, Autoimmune disease, others

No Placebo Group

Breakthrough Therapy

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.

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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.

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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.

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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

Trial 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

Participant Groups

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.

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mayo Clinic in Arizona Scottsdale, AZ

Mayo Clinic in Florida Jacksonville, FL

Mayo Clinic in Rochester Rochester, MN

Who Is Running the Clinical Trial?

Mayo Clinic Lead Sponsor

NanoPass Technologies Ltd Industry Sponsor

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] In ovarian cancer (OC), IL-17-producing T cells (Th17s) predict improved survival, whereas regulatory T cells predict poorer survival. We previously developed a vaccine whereby patient-derived dendritic cells (DCs) are programmed to induce Th17 responses to the OC antigen folate receptor alpha (FRα). Here we report the results of a single-arm open-label phase I clinical trial designed to determine vaccine safety and tolerability (primary outcomes) and recurrence-free survival (secondary outcome). Immunogenicity is also evaluated. Recruitment is complete with a total of 19 Stage IIIC-IV OC patients in first remission after conventional therapy. DCs are generated using our Th17-inducing protocol and are pulsed with HLA class II epitopes from FRα. Mature antigen-loaded DCs are injected intradermally. All patients have completed study-related interventions. No grade 3 or higher adverse events are seen. Vaccination results in the development of Th1, Th17, and antibody responses to FRα in the majority of patients. Th1 and antibody responses are associated with prolonged recurrence-free survival. Antibody-dependent cell-mediated cytotoxic activity against FRα is also associated with prolonged RFS. Of 18 patients evaluable for efficacy, 39% (7/18) remain recurrence-free at the time of data censoring, with a median follow-up of 49.2 months. Thus, vaccination with Th17-inducing FRα-loaded DCs is safe, induces antigen-specific immunity, and is associated with prolonged remission.

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

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022] To evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer.

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] To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)-expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial.

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] To describe the clinical outcomes associated with the use of checkpoint inhibitor therapy in recurrent ovarian malignancy.

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] Immune checkpoint inhibitors (ICIs) to date have demonstrated limited activity in advanced ovarian cancer (OC). Folate receptor alpha (FRα) is overexpressed in the majority of OCs and presents an attractive target for a combination immunotherapy to potentially overcome resistance to ICI in OCs. The current study sought to examine clinical and immunologic responses to TPIV200, a multiepitope FRα vaccine administered with programmed death ligand 1 (PD-L1) inhibitor durvalumab in patients with advanced platinum-resistant OC.

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] Anti-programmed death 1 (PD1)/programmed cell death ligand 1 (PD-L1) therapies have shown modest activity as monotherapy in recurrent ovarian cancer. Platinum chemotherapies induce T-cell proliferation and enhance tumor recognition. We assessed activity and safety of pembrolizumab with carboplatin in recurrent platinum-resistant ovarian cancer.

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

Oligopeptides for Immunotherapy Approaches in Ovarian Cancer Treatment. [2020] Anti-ovarian cancer vaccines based on minimal immune determinants uniquely expressed in ovarian cancer biomarkers appear to promise a high level of sensitivity and specificity for ovarian cancer immunodiagnostics, immunoprevention, and immunotherapy.