Cancer Vaccine for BRCA Gene Mutation

Overseen By Alex Torres

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must not be taking: Systemic steroids, Immunosuppressive therapy

Disqualifiers: HIV, Hepatitis B/C, Pregnancy, others

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

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a vaccine called INO-5401 to determine its potential in preventing cancer in individuals with BRCA1 or BRCA2 gene mutations. The study aims to assess the vaccine's safety and its ability to activate the immune system against cancer. Participants are divided into two groups: one receives only INO-5401, while the other receives INO-5401 with an additional component, INO-9012. Suitable candidates include those with a BRCA1 or BRCA2 mutation who have had cancers such as breast, ovarian, pancreatic, or prostate cancer and have completed treatment with no signs of the disease. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic steroids or immunosuppressive therapy at least 4 weeks before starting the study treatment. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team.

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

Research shows that INO-5401, a cancer vaccine, is designed to help the immune system target cancer cells in people with BRCA gene mutations. Early results suggest that this vaccine, both alone and with another compound called INO-9012, is generally safe, as most participants did not experience serious side effects during initial testing.

Researchers have studied the combination of INO-5401 and INO-9012 to assess its safety. Early studies focused on monitoring side effects and testing a new delivery method called electroporation, which uses a small electrical pulse to help the vaccine enter cells. So far, these methods appear safe.

While more research is needed to confirm these findings, early data is promising for those considering joining the trial. It suggests that the vaccines are safe, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about INO-5401 because it represents a novel approach to treating cancers associated with BRCA gene mutations. Unlike traditional therapies like chemotherapy, INO-5401 is a DNA-based cancer vaccine designed to stimulate the immune system to specifically target cancer cells. This treatment is administered through electroporation, a method that enhances the uptake of the vaccine by cells, potentially leading to a more robust immune response. Additionally, the combination of INO-5401 with INO-9012 aims to further boost the immune system's ability to fight cancer, offering a promising new avenue for patients with limited options.

What evidence suggests that this trial's treatments could be effective for BRCA gene mutation?

Research shows that INO-5401, a cancer vaccine, aims to prevent cancer in people with BRCA1 or BRCA2 mutations by helping the immune system attack cancer cells. The vaccine includes certain genes often active in many cancers, making them good targets for the immune system. In this trial, some participants will receive INO-5401 alone, while others will receive a combination of INO-5401 and INO-9012. Earlier studies on similar vaccines have shown promise by boosting immune responses. Early results suggest that when used with INO-9012, it is safe and can effectively stimulate the immune system. While specific results for INO-5401 alone are limited, the research relies on strong scientific principles that have shown potential in related treatments. ^{1 3 4 6 7}

Who Is on the Research Team?

Susan Domchek, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 18 with BRCA1 or BRCA2 mutations who've had breast, ovarian, pancreatic (excluding neuroendocrine), or prostate cancer but are now free of disease. Participants must have completed adjuvant therapy and be post-menopausal if female. They should not have significant heart issues, bleeding disorders, active infections like HIV or hepatitis B/C, recent major surgery, or require steroids/immunosuppressants.

Inclusion Criteria

Signed and dated IRB approved informed consent

My liver, kidneys, and bone marrow are functioning normally.

I have at least 2 clear areas on my skin suitable for injections.

Exclusion Criteria

I have a condition that causes early heartbeats.

Any illness or condition that in the opinion of the investigator may affect the safety of the subject or the evaluation of any study endpoint

Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive INO-5401 and INO-9012 vaccines, followed by electroporation, on Day 1, Week 4, Week 8, and Week 12

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• INO-5401

Trial Overview The study tests an experimental vaccine called INO-5401 to prevent cancer in individuals with BRCA gene mutations. It examines the vaccine's safety and immune system activation using a new delivery method involving Cellectra 2000 alongside another agent named INO-9012.

How Is the Trial Designed?

Group I: INO-5401 and INO-9012 Experimental Treatment 3 Interventions

Participants receive INO-5401 and INO-09012 vaccine, followed by electroporation, on Day 1, Week 4, Week 8, and Week 12

Group II: INO-5401 Experimental Treatment 2 Interventions

Participants receive INO-5401 vaccine, followed by electroporation, on Day 1, Week 4, Week 8, and Week 12

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Inovio Pharmaceuticals

Industry Sponsor

Trials

54

Recruited

4,800+

Published Research Related to This Trial

NY-ESO-1 is commonly found in epithelial ovarian cancer and can trigger immune responses, making it a promising target for cancer vaccines.

Two novel NY-ESO-1-derived epitopes were identified that can activate both CD4+ and CD8+ T cells, suggesting they could enhance immune responses in patients and serve as potential vaccine candidates for a broader range of cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recognition of naturally processed and ovarian cancer reactive CD8+ T cell epitopes within a promiscuous HLA class II T-helper region of NY-ESO-1. Matsuzaki, J., Qian, F., Luescher, I., et al.[2020]

Personalized neoantigen-based cancer vaccines are safe and effective, but their manufacturing can be expensive and slow; using off-the-shelf vaccines targeting shared neoantigens could solve these issues.

The study identified specific recurrent mutations in BRCA1-positive and BRCA1-negative breast cancer samples, providing a list of potential shared neoantigens that could be used to develop more accessible cancer vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Shared Neoantigens in BRCA1-Related Breast Cancer. Ruangapirom, L., Sutivijit, N., Teerapakpinyo, C., et al.[2022]

The cancer testis antigen Sp17 is linked to tumor progression in epithelial ovarian cancer (EOC), as it enables tumor formation in vivo despite not affecting cell growth in vitro.

Sp17-positive cells exhibit higher levels of immunosuppressive markers like PD-L1 and STAT3, which contribute to their resistance to chemotherapy (Paclitaxel), making Sp17 a promising target for vaccine development against EOC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sperm Protein 17 Expression by Murine Epithelial Ovarian Cancer Cells and Its Impact on Tumor Progression. Gao, Q., Xiang, SD., Wilson, K., et al.[2020]

The NY-ESO-1 vaccine, formulated with the ISCOMATRIX adjuvant, effectively stimulates the immune system by inducing NY-ESO-1-specific CD8(+) T cells and CD4(+) T cells, demonstrating strong immunogenicity in preclinical models.

In C57BL/6 mice, the vaccine not only generated robust immune responses but also provided protection against tumors expressing NY-ESO-1, indicating its potential as a powerful therapeutic anticancer vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NY-ESO-1 protein formulated in ISCOMATRIX adjuvant is a potent anticancer vaccine inducing both humoral and CD8+ t-cell-mediated immunity and protection against NY-ESO-1+ tumors. Maraskovsky, E., Sjölander, S., Drane, DP., et al.[2019]

In a study of 816 cancer patients, the BNT162b2 vaccine demonstrated a high serologic response rate of 94.2% after the second dose, indicating effective immunization against COVID-19.

The vaccine was well tolerated, with only 3.5% and 1.3% of patients experiencing severe adverse events after the first and second doses, respectively, suggesting it is safe for use in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and Safety of COVID-19 Vaccine BNT162b2 for Patients with Solid Cancer: A Large Cohort Prospective Study from a Single Institution. Di Noia, V., Pimpinelli, F., Renna, D., et al.[2021]

Breast cancer (BC) treatment is evolving towards personalized medicine that enhances the patient's immune system to combat cancer, as traditional therapies still face challenges with mortality and relapse rates.

Promising early-phase clinical trials of BC vaccines like NeuVax, AVX901, and INO-1400 indicate that immunotherapy could be a highly effective strategy, although further optimization in various aspects is necessary for improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast Cancer Vaccines: New Insights. Benedetti, R., Dell'Aversana, C., Giorgio, C., et al.[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]

In a long-term follow-up of 15 patients with advanced non-small cell lung cancer (NSCLC) treated with an IDO peptide vaccine, 20% of patients (3 out of 15) are still alive after 6 years, indicating potential long-term efficacy of the treatment.

The vaccine was well tolerated over 5 years with no long-term toxicities, and two patients showed significant clinical responses, including one with a partial response that has been maintained for over 5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable Clinical Responses and Long-Term Follow-Up of Stage III-IV Non-Small-Cell Lung Cancer (NSCLC) Patients Treated With IDO Peptide Vaccine in a Phase I Study-A Brief Research Report. Kjeldsen, JW., Iversen, TZ., Engell-Noerregaard, L., et al.[2019]

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]

In a phase I clinical trial involving 18 patients with epithelial ovarian cancer, immunization with the NY-ESO-1 peptide ESO(157-170) successfully induced specific immune responses without serious adverse events, highlighting its safety and potential efficacy.

The study demonstrated that providing CD4+ T cell help enhances the immune response against tumors, with long-lasting and functional T cell responses observed in some patients up to 12 months post-vaccination, supporting further investigation in a phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T cell responses in ovarian cancer. Odunsi, K., Qian, F., Matsuzaki, J., et al.[2021]

Vaccination with the NY-ESO-1b peptide in high-risk epithelial ovarian cancer patients resulted in minimal toxicity, with no severe adverse events (grade 3 or 4), and only mild to moderate side effects such as fatigue and hypothyroidism.

The treatment successfully induced specific T-cell immunity in a significant portion of patients, with 75% of NY-ESO-1-positive and 80% of NY-ESO-1-negative patients showing immune responses, suggesting potential effectiveness in both tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity study of NY-ESO-1b peptide and montanide ISA-51 vaccination of patients with epithelial ovarian cancer in high-risk first remission. Diefenbach, CS., Gnjatic, S., Sabbatini, P., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04367675

INO 5401 Vaccination in BRCA1/2 Mutation Carriers The research study is being conducted to test an experimental vaccine to potentially prevent cancer for people with BRCA1 or BRCA2 mutations.

2. withpower.com withpower.com/trial/phase-1-3-2021-e2f16

Cancer Vaccine for BRCA Gene Mutation Although specific data on INO-5401 is not provided, similar vaccines have shown promise in early trials by improving immune responses and potentially enhancing ...

3. newsroom.clevelandclinic.org newsroom.clevelandclinic.org/2024/11/08/cleveland-clinic-announces-updated-findings-in-preventive-breast-cancer-vaccine-study

Cleveland Clinic Announces Updated Breast Cancer ... The study team found that the investigational vaccine was generally well tolerated and produced an immune response in most patients. The team ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-03929

Vaccine Therapy (INO-5401 with or without INO-9012) ... INO-5401 contains genes which are active in human cancers (hTERT, PMSA, and WNT1) and are felt to be good targets for the immune system for both people who have ...

5. protocols.io protocols.io/view/development-of-mrna-based-vaccination-for-brca1-mu-dmej43cn

Development of mRNA-Based Vaccination for BRCA1- ... This study aims to evaluate the safety, efficacy, and optimal dosing of an mRNA-based therapy encoding the BRCA1 gene in patients with advanced BRCA1-mutated ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.10505

IL12 (INO-9012) followed by electroporation in cancer ... We evaluated an immunological approach for cancer interception via a DNA plasmid vaccine. INO-5401 is a recombinant plasmid-derived DNA based ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9609887/

Identification of Shared Neoantigens in BRCA1-Related ... Personalized neoantigen-based cancer vaccines have been shown to be safe and immunogenic in cancer patients; however, the manufacturing process can be costly ...