NY-ESO-1 Vaccine + Nivolumab for Ovarian Cancer

Recruiting at 2 trial locations

Overseen By Nicole Swanson

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Georgetown University

Must not be taking: Immunosuppressants, PD-1 antagonists

Disqualifiers: Autoimmune disease, Active infection, others

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a vaccine that helps the immune system fight cancer in patients with advanced ovarian cancer who don't respond to standard treatments. The vaccine aims to make other treatments more effective by preventing resistance. Special immune cells are used in this therapy.

Will I have to stop taking my current medications?

The trial requires that any hormonal therapy for the cancer be stopped at least one week before joining, and any other cancer treatments be stopped at least four weeks before. However, you can continue using hormones for non-cancer conditions, like insulin for diabetes.

What data supports the effectiveness of the NY-ESO-1 Vaccine + Nivolumab treatment for ovarian cancer?

Research shows that the NY-ESO-1 vaccine can trigger strong immune responses in ovarian cancer patients, helping the body's immune system recognize and attack cancer cells. Additionally, the combination of NY-ESO-1 with other immune-boosting agents has shown promise in enhancing these responses, suggesting potential effectiveness in treating ovarian cancer. ^{1 2 3 4 5}

Is the NY-ESO-1 vaccine combined with Nivolumab safe for humans?

The NY-ESO-1 vaccine has been tested in humans and is generally well tolerated, with common side effects being mild fever and injection site reactions. Nivolumab, also known as Opdivo, has been used in various cancer treatments and is considered safe, though it may cause side effects like fatigue and skin rash. ^{1 6 7 8 9}

How is the NY-ESO-1 Vaccine + Nivolumab treatment different from other ovarian cancer treatments?

This treatment is unique because it combines a vaccine targeting the NY-ESO-1 antigen, which is present in many ovarian cancers, with Nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This combination aims to enhance the body's immune response against the cancer, which is different from traditional chemotherapy that directly targets cancer cells. ^{1 2 6 7 10}

Research Team

Samir N Khleif, MD

Principal Investigator

Georgetown University

Eligibility Criteria

This trial is for women aged 18 or older with stage III/IV platinum-refractory ovarian cancer who have progressed on standard treatment, including those with BRCA mutations. Participants must have recovered from recent surgery or therapy, not be on active infection antibiotics (except simple UTI), and agree to use effective contraception. Exclusions include prior nivolumab or similar therapies, autoimmune diseases within the past 2 years, other concurrent clinical trials, and certain medical conditions.

Inclusion Criteria

You have fully recovered from any recent surgery, radiotherapy, or chemotherapy.

Subjects will be eligible for study entry based on the following diagnostic workup: History/physical examination within 28 days prior to registration, Imaging of target lesion(s) within 28 days prior to registration, Recovery from effects of recent surgery, radiotherapy or chemotherapy, Free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection), Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration, Any other prior therapy directed at the malignant tumor including chemotherapy, targeted agents, biologic agents, immunologic agents, and any investigational agents, must be discontinued at least 4 weeks prior to registration (6 weeks for nitrosoureas or mitomycin C), Any prior radiation therapy must be completed at least 4 weeks prior to registration, At least 4 weeks must have elapsed since major surgery, Subjects must have received and have progressed, are refractory, or are intolerant to standard platinum therapy, Subjects should not have received more than 2 prior lines of systemic therapy for recurrent or metastatic disease (including both standard of care and investigational therapies), Subjects must have at least 1 lesion that is measurable using RECIST Version 1.1 guidelines, A previously irradiated lesion can be considered a target lesion if the lesion is well defined, measurable per RECIST Version 1.1, and has clearly progressed, Subjects undergoing fresh tumor biopsies must have additional non-target lesions that can be biopsied at acceptable risk as judged by the investigator (optional), Subjects must consent to provide archived tumor specimens for correlative biomarker studies, Tumor tissue must be identified and availability confirmed prior to initiation of study therapy, In the setting where archival material is unavailable or unsuitable for use, subjects must consent and undergo fresh tumor biopsy, All subjects are encouraged to consent to and provide both pretreatment and on-treatment (optional) tumor biopsies, Eastern Cooperative Oncology Group (ECOG) Performance score of 2 or less, In the opinion of the investigator likely to complete ≥ 8 weeks of treatment, Adequate organ function as determined by: Hematological, Renal, Hepatic, Female subjects of childbearing potential who are sexually active with a nonsterilized male partner must use at least 1 highly effective method of contraception from screening, and must agree to continue using such precautions for 180 days after the final dose of investigational product, Females of childbearing potential are defined as those who are not surgically sterile (i.e., have not undergone bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or who are not postmenopausal (defined as 12 months with no menses without an alternative medical cause), A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, Subjects must refrain from breastfeeding while on study and for 180 days after the final dose of investigational product

Be able and willing to provide written and signed informed consent prior to performing any protocol-related procedures, including screening evaluations

Exclusion Criteria

You have had a very severe allergic reaction to any unknown allergens or any components of the study drug formulations.

Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results

You have had an autoimmune disease like Crohn's disease or lupus in the past 2 years. If you have conditions like asthma or vitiligo, or if your autoimmune disease is stable with hormone or steroid replacement, you are not excluded.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NY-ESO-1 peptide vaccine and Toripalimab-tpzi to prevent anti-PD1 resistance

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Nivolumab
• NY-ESO-1 Peptide vaccine

Trial Overview The study tests a combination of NY-ESO-1 Peptide vaccine and Nivolumab in patients with advanced ovarian cancer resistant to platinum-based chemotherapy. It's an open-label phase II trial aiming to prevent resistance to anti-PD-1 therapy by using the vaccine as a priming agent before administering Nivolumab.

Participant Groups

Group I: NY-ESO-1 Peptide vaccine plus Toripalimab-tpzi Experimental Treatment 2 Interventions

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

Coherus Biosciences, Inc.

Industry Sponsor

Trials

19

Recruited

3,700+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

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]

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]

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 cohort A, which included 30 patients with metastatic melanoma, the combination of an IDO/PD-L1 vaccine and nivolumab resulted in an impressive overall response rate of 80%, with 50% achieving a complete response and a median progression-free survival of 25.5 months.

Cohort B, where the vaccine was added to patients already on anti-PD-1 therapy, showed limited efficacy with only stable disease in 2 out of 10 patients and a median progression-free survival of just 2.4 months, indicating that the combination may not be effective for those with progressive disease during anti-PD-1 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of anti-PD-1 naïve patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab. Lorentzen, CL., Kjeldsen, JW., Ehrnrooth, E., et al.[2023]

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. 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]

2. 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]

3. Japan pubmed.ncbi.nlm.nih.gov

[Immune monitoring and cancer vaccine]. [2012]

4. New Zealand pubmed.ncbi.nlm.nih.gov

NY-ESO-1 Protein Vaccine Combining Alum, CpG ODN, and HH2 Complex Adjuvant Induces Protective and Therapeutic Anti-Tumor Responses in Murine Multiple Myeloma. [2022]

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

Vaccination with NY-ESO-1 overlapping peptides mixed with Picibanil OK-432 and montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen. [2021]

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

A phase I study of vaccination with NY-ESO-1f peptide mixed with Picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen. [2020]

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

Long-term follow-up of anti-PD-1 naïve patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab. [2023]

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

LUD 00-009: phase 1 study of intensive course immunization with NY-ESO-1 peptides in HLA-A2 positive patients with NY-ESO-1-expressing cancer. [2021]

10. 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]