Vigil Vaccine for Ovarian Cancer

(VITAL Trial)

Recruiting at 33 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Gradalis, Inc.

Must be taking: Platinum, Taxane

Must not be taking: Immunosuppressants, Chronic steroids

Disqualifiers: Heart disease, Brain metastases, Autoimmune, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 months

92 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive therapy or chronic steroids, you may need to stop them before joining the trial.

What data supports the effectiveness of the Vigil Vaccine treatment for ovarian cancer?

Research shows that cancer vaccines, like the Vigil Vaccine, can trigger immune responses that target cancer cells, and there is evidence that these immune responses are linked to better outcomes in some cancer patients. Although no Phase III trials have shown a clear benefit for ovarian cancer yet, improvements in vaccine design and understanding of the immune system are promising for future success. ^{1 2 3 4 5}

Is the Vigil vaccine safe for humans?

The Vigil vaccine, when combined with atezolizumab, was found to be safe in a study with ovarian cancer patients, with fewer severe treatment-related side effects compared to the alternative treatment sequence. ^{1 2 6 7 8}

How is the Vigil treatment different from other ovarian cancer treatments?

Vigil is a personalized vaccine that uses a patient's own tumor cells to enhance the immune system's response against ovarian cancer, making it unique compared to standard treatments. It works by increasing tumor neoantigen expression and controlling immune-suppressing factors, which may improve survival, especially in patients without BRCA mutations. ^{1 8 9 10 11}

What is the purpose of this trial?

The goal of this clinical trial is to compare participants with ovarian, fallopian tube or primary peritoneal cancer when treated with investigational product (Vigil) compared to placebo. The main question it aims to answer is "Will participants who receive treatment with Vigil have a longer time to disease recurrence versus the participants that were not given Vigil?"

Research Team

John Nemunaitis, MD

Principal Investigator

Gradalis, Inc.

Eligibility Criteria

This trial is for women aged 18 or older with Stage IIIb, IIIc, or IV high-grade ovarian, fallopian tube, or primary peritoneal cancer. They must have completed surgery and chemotherapy without prior hypersensitivity to those treatments and be in clinical complete response. Participants need normal organ function and no history of certain diseases like autoimmune disorders or recent heart issues.

Inclusion Criteria

I was able to care for myself before my surgery.

My cancer is not detectable after surgery and chemotherapy.

I started chemotherapy within 8 weeks after my initial surgery.

Exclusion Criteria

I have HIV or chronic Hepatitis B or C.

My cancer is a specific type that affects the uterus.

I have serious heart issues, including recent heart failure, unstable chest pain, or a recent heart attack.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Vigil or placebo by intradermal injection every 4 weeks for a minimum of 4 and up to a maximum of 6 doses

4-6 months

Monthly visits for injections

Follow-up

Participants are monitored for disease recurrence and overall survival with imaging assessments every 3 months in Years 1-3, every 6 months in Years 4-5, and yearly through Year 10

10 years

Long-term follow-up

Participants enter long-term follow-up for survival status and post-treatment therapies received upon recurrence

Treatment Details

Interventions

• Placebo
• Vigil

Trial Overview The study tests Vigil, an investigational product against a placebo in patients who've had ovarian-related cancers. It aims to see if Vigil extends the time before the disease comes back compared to not receiving it. Patients are randomly assigned to receive either Vigil or a placebo.

Participant Groups

Group I: Group A Active Control 1 Intervention

Vigil immunotherapy will be administered at a concentration of 1.0 x 10e7 cells/dose given via intradermal injection every 4 weeks for a minimum of 4 and a maximum of 6 administrations as determined by the number of doses manufactured and as long as the subject is clinically stable and recurrence free.

Group II: Group B Placebo Group 1 Intervention

Placebo will be administered via intradermal injection every 4 weeks for a minimum of 4 and a maximum of 6 administrations as determined by the number of doses manufactured and as long as the subject is clinically stable and recurrence free.

Who Is Running the Clinical Trial?

Gradalis, Inc.

Lead Sponsor

Trials

16

Recruited

490+

Findings from Research

Recent trials have shown that antitumor vaccines can improve progression-free survival in breast cancer and overall survival in prostate cancer, marking a significant advancement in solid tumor vaccine therapy.

While no positive Phase III trials for ovarian cancer vaccines have been reported yet, ongoing improvements in target antigens and antigen presentation, along with new biological therapies, hold promise for enhancing vaccine efficacy in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian cancer vaccine trials and tribulations. Buckanovich, RJ.[2019]

Ovarian cancer patients often face poor survival rates, with less than 40% surviving past 5 years, highlighting the urgent need for effective treatments like cancer vaccines that can stimulate T cell responses.

Using the murine ID8 ovarian tumor model, the study shows that combining cancer vaccines with standard treatments can enhance overall efficacy, suggesting a promising approach for improving outcomes in ovarian cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating Cancer Vaccines in the Standard-of-Care of Ovarian Cancer: Translating Preclinical Models to Human. Chiang, CL., Rovelli, R., Sarivalasis, A., et al.[2021]

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 study involved 21 patients with high-grade serous ovarian cancer treated with a vaccine and bevacizumab, showing that the treatment was generally well tolerated, with only one case of severe toxicity and a small percentage experiencing significant side effects.

While the vaccine induced an immunogenic response in a majority of patients, this response did not correlate with improved survival outcomes, although increased levels of IL-8 were linked to better progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of patients with recurrent ovarian cancer treated with a polyvalent vaccine with bevacizumab combination. Kahn, RM., Ragupathi, G., Zhou, QC., et al.[2023]

The combination of the Vigil vaccine and atezolizumab was found to be safe for patients with relapsed ovarian cancer, with no dose-limiting toxicities reported in the initial safety assessment involving 3 patients.

Patients receiving the Vigil vaccine first (Vigil-1st) showed a significantly improved median overall survival compared to those starting with atezolizumab (Atezo-1st), with a hazard ratio of 0.33, indicating a potential benefit for further investigation, especially in BRCA wild-type patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proof of principle study of sequential combination atezolizumab and Vigil in relapsed ovarian cancer. Rocconi, RP., Stevens, EE., Bottsford-Miller, JN., et al.[2022]

References

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

Therapeutic vaccines for ovarian cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Ovarian cancer vaccine trials and tribulations. [2019]

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

Immunological monitoring of anticancer vaccines in clinical trials. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Integrating Cancer Vaccines in the Standard-of-Care of Ovarian Cancer: Translating Preclinical Models to Human. [2021]

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Development of Therapeutic Vaccines for Ovarian Cancer. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Long-term outcomes of patients with recurrent ovarian cancer treated with a polyvalent vaccine with bevacizumab combination. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Proof of principle study of sequential combination atezolizumab and Vigil in relapsed ovarian cancer. [2022]

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

A novel breast/ovarian cancer peptide vaccine platform that promotes specific type-1 but not Treg/Tr1-type responses. [2020]

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

Phase II study of Vigil® DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer. [2017]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Gemogenovatucel-T (Vigil) immunotherapy for advanced ovarian carcinoma: A systematic review and meta-analysis of randomized controlled trials. [2022]