Cancer Vaccine for BRCA Gene Mutation

Overseen by Susan Domchek, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Pennsylvania

Must not be taking: Systemic steroids, Immunosuppressive therapy

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new vaccine to prevent cancer in people with BRCA1 or BRCA2 mutations. The vaccine aims to boost the immune system to help it fight off cancer cells. It is currently being evaluated for its effectiveness.

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.

What data supports the effectiveness of the treatment INO-5401 for BRCA gene mutation?

Research on cancer vaccines, like those for breast and ovarian cancer, shows that they can stimulate the immune system to fight cancer cells. Although specific data on INO-5401 is not provided, similar vaccines have shown promise in early trials by improving immune responses and potentially enhancing survival in cancer patients. ^{1 2 3 4 5}

Is the cancer vaccine for BRCA gene mutation generally safe in humans?

The IDO peptide vaccine, which may be similar to the cancer vaccine for BRCA gene mutation, was well tolerated in a study with non-small-cell lung cancer patients, showing no long-term toxicities over 5 years. ^{6 7 8 9 10}

How is the treatment INO-5401 unique for BRCA gene mutation-related cancer?

INO-5401 is a cancer vaccine that aims to stimulate the immune system to target cancer cells with BRCA gene mutations, which is different from traditional treatments like chemotherapy that directly attack cancer cells. This approach is novel because it uses the body's own immune response to fight cancer, potentially offering a more targeted and less toxic treatment option. ^{1 5 7 10 11}

Research Team

Susan Domchek, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Eligibility Criteria

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 am 18 years old or older.

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

Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation; continued participation in an observational study is allowed

Trial Timeline

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

Treatment Details

Interventions

• INO-5401 (Cancer Vaccine)

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.

Participant Groups

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+

Dr. Joan Lau

University of Pennsylvania

Chief Executive Officer since 2020

PhD in Neuroscience from the University of Cincinnati College of Medicine, MBA from the Wharton School of Business, BS in Bioengineering from the University of Pennsylvania

Dr. Robert Iannone

University of Pennsylvania

Chief Medical Officer since 2019

MD from Yale University, MSCE from the University of Pennsylvania

Inovio Pharmaceuticals

Industry Sponsor

Trials

54

Recruited

4,800+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Identification of Shared Neoantigens in BRCA1-Related Breast Cancer. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Breast Cancer Vaccines: New Insights. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Ovarian cancer vaccine trials and tribulations. [2019]

5. United States 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. [2021]

6. Switzerland 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. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Sperm Protein 17 Expression by Murine Epithelial Ovarian Cancer Cells and Its Impact on Tumor Progression. [2020]

8. United States 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. [2023]

9. United States 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. [2021]

10. Germany 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. [2020]

11. United States 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. [2019]