Vaccines for Advanced Melanoma

(TdVax Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Georgia Beasley, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Duke University

Must be taking: PD-1 therapy

Must not be taking: Chronic steroids

Disqualifiers: Pregnancy, HIV, Hepatitis B, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the safety and feasibility of administering the Tetanus Diptheria Vaccine (Td) or Polio Boost Immunization (IPOL) to patients with metastatic melanoma who are receiving immune checkpoint inhibitor (IO) therapy per standard of care. Subjects will have the vaccine at cycle 4 of IO therapy and will have research blood and tissue samples collected prior to starting IO therapy, at cycle 4 prior to vaccine administration, and at 12-17 days post vaccine.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, if you are on immunosuppressive therapy or steroids above a certain dose, you may not be eligible to participate.

What data supports the effectiveness of the treatment Polio Boost Immunization, IPOL, Poliovirus Vaccine, Inactivated, Tetanus Diptheria Vaccine, Td Vaccine, Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap), Diphtheria and Tetanus Toxoids Adsorbed (DT) for advanced melanoma?

Research suggests that melanoma vaccines can stimulate immune responses that may improve clinical outcomes in patients with advanced melanoma. Additionally, vaccines like the vaccinia melanoma oncolysate have shown increased survival rates in melanoma patients, indicating potential benefits of vaccine-based treatments. ^{1 2 3 4 5}

Is the vaccine for advanced melanoma safe for humans?

The safety of the melanoma vaccines has been evaluated in various studies. A vaccine containing melanoma-associated peptides was found to be safe in a phase I/II trial. Additionally, the Oncept melanoma vaccine, used in veterinary medicine, appears safe, although its effectiveness is debated. ^{2 6 7 8 9}

How does the melanoma vaccine treatment differ from other treatments for advanced melanoma?

The melanoma vaccine treatment is unique because it aims to stimulate the body's immune system to fight melanoma cells, potentially improving survival rates for patients with advanced melanoma. Unlike traditional treatments, these vaccines have relatively low toxicity, making them suitable for use even in early-stage patients at high risk of recurrence. ^{1 2 3 10 11}

Research Team

Georgia Beasley, MD

Principal Investigator

Duke University

Eligibility Criteria

This trial is for adults with advanced metastatic melanoma who are about to start or are already on PD-1 therapy or combined PD-1 and anti CTLA-4 therapy. They must have at least one lesion suitable for biopsy, good organ function, and no history of certain conditions like uveal/mucosal melanoma, active pneumonitis requiring steroids, known HIV infection, recent Td vaccine receipt within 30 days before IO therapy, immunodeficiency states or systemic steroid use.

Inclusion Criteria

I am 18 years or older and have given my consent.

Your hemoglobin level is 9.0 grams per deciliter or higher.

I have a visible or palpable tumor lesion that is at least 8 mm.

Exclusion Criteria

History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with subject's participation for the full duration of the study, or make it not in the best interest of the subject to participate, in the opinion of the treating physician

I am currently on medication for an infection.

I have an active tuberculosis infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immune checkpoint inhibitor (IO) therapy and a Td or IPOL vaccine at cycle 4

4-5 months

Multiple visits for IO therapy cycles and vaccine administration

Follow-up

Participants are monitored for safety and effectiveness after vaccine administration

8-12 weeks post vaccine

SOC scan following vaccine

Long-term follow-up

Preliminary efficacy assessed by objective response rate up to 36 months

up to 36 months

Treatment Details

Interventions

• Polio Boost Immunization (Cancer Vaccine)
• Tetanus Diptheria Vaccine (Cancer Vaccine)

Trial Overview The study tests the safety and feasibility of giving a Tetanus Diptheria Vaccine (Td) or Polio Boost Immunization (IPOL) alongside standard immune checkpoint inhibitor therapies in patients with metastatic melanoma. It aims to see if these vaccines can boost the body's immune response when given during cycle 4 of IO therapy.

Participant Groups

Group I: Td Vaccine Experimental Treatment 1 Intervention

The first 15 subjects enrolled will receive the Td (tetanus diphtheria) vaccine at cycle 4 of IO therapy. The Td vaccine is administered as 0.5 mL intramuscular injection in the extremity (thigh or upper arm) in closest proximity to the largest tumor.

Group II: IPOL Vaccine Experimental Treatment 1 Intervention

Subjects 16 through 25 will receive the IPOL (polio booster) vaccine at cycle 4 of IO therapy. The IPOL vaccine is administered as 0.5 mL intramuscular or subcutaneous injection in the extremity (thigh or upper arm) in closest proximity to the largest tumor

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Mary E. Klotman

Duke University

Chief Executive Officer since 2017

MD from Duke University School of Medicine

Michelle McMurry-Heath

Duke University

Chief Medical Officer since 2020

MD from Duke University School of Medicine

Findings from Research

Melanoma vaccines are considered an experimental treatment for patients who have had surgery to remove melanoma but are at high risk of recurrence, as well as for some patients with advanced disease.

There is a positive correlation between the ability of these vaccines to stimulate immune responses against melanoma and improved clinical outcomes, leading to ongoing phase III studies to better assess their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccines for melanoma. Bystryn, JC.[2019]

In a phase III trial involving 217 patients with surgically resected stage II melanoma, the vaccinia melanoma oncolysate (VMO) vaccine did not show a significant overall survival benefit compared to a placebo vaccine.

However, specific subsets of patients, particularly males aged 44-57 with one to five positive lymph nodes and those with clinical stage I melanoma, demonstrated a significant survival advantage when treated with VMO, indicating potential targeted efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival of patients treated with a vaccinia melanoma oncolysate vaccine: second interim analysis of data from a phase III, multi-institutional trial. Wallack, MK., Sivanandham, M., Ditaranto, K., et al.[2020]

Two MUC1 tetanus toxoid vaccines were developed that successfully triggered a strong immune response in mice, indicating their potential as effective cancer treatments.

The antibodies produced by these vaccines specifically target tumor cells in mammary carcinoma tissues and can differentiate between tumors at various stages, suggesting a tailored approach to cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthetic antitumor vaccines containing MUC1 glycopeptides with two immunodominant domains-induction of a strong immune response against breast tumor tissues. Gaidzik, N., Kaiser, A., Kowalczyk, D., et al.[2012]

In a phase II trial with 43 patients with early melanoma, vaccination with modified tumor peptides led to a significant increase in specific CD8(+) T cells in 75% of participants, indicating a robust immune response.

Despite the immune activation, the vaccination did not improve disease-free or overall survival compared to the observation group, suggesting that the induced T cells had limited effectiveness against melanoma cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited induction of tumor cross-reactive T cells without a measurable clinical benefit in early melanoma patients vaccinated with human leukocyte antigen class I-modified peptides. Filipazzi, P., Pilla, L., Mariani, L., et al.[2020]

The TLPLDC vaccine was well-tolerated in a phase IIb trial with 144 patients, showing similar toxicity levels compared to the placebo group, indicating a good safety profile for this treatment.

In patients who completed the primary vaccine series, the TLPLDC vaccine significantly improved disease-free survival at 24 months (62.9% vs. 34.8%) compared to the placebo, suggesting it may effectively help prevent recurrence in resected stage III/IV melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis. Vreeland, TJ., Clifton, GT., Hale, DF., et al.[2022]

The combination of the 6MHP vaccine and pembrolizumab was found to be safe, with manageable side effects, and it successfully increased the number of immune cells in tumors, which is a positive sign for cancer treatment.

In patients who had not previously received PD-1 antibody treatment, the vaccine led to a significant objective response rate of 67%, suggesting that this approach may be particularly effective in early treatment stages for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II clinical trial of a helper peptide vaccine plus PD-1 blockade in PD-1 antibody-naïve and PD-1 antibody-experienced patients with melanoma (MEL64). Vavolizza, RD., Petroni, GR., Mauldin, IS., et al.[2022]

The Oncept melanoma vaccine, which targets the tyrosinase protein, is approved for treating stage II to III canine oral melanoma and is considered safe for use in dogs.

Despite its safety, the evidence regarding its effectiveness in improving survival rates is inconsistent, leading to controversy within the veterinary oncology community.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Oncept Melanoma Vaccine in Veterinary Patients: A Review of the Literature. Pellin, MA.[2022]

In a study involving 45 immunocompetent patients with solid tumors, significant morbidity was observed from the immunization with BCG, PPD, and tumor cells, including painful ulcerations and potential tumor growth enhancement in some patients.

Despite the adverse effects, the treatment led to notable changes in cellular immunity, such as enhanced skin reactions to microbial antigens and evidence of immunologic memory, but did not result in significant regression of untreated tumor lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility study of active immunotherapy in patients with solid tumors. Gerner, RE., Moore, GE.[2019]

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]

Melanoma vaccines show promise as a treatment option for patients with advanced melanoma, potentially improving survival rates.

Due to their low toxicity, these vaccines may also be beneficial as adjuvant therapy for stage I melanoma patients who are at high risk for recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melanoma vaccines. Naylor, MF.[2007]

Vaccination with peptide mimotopes of the melanoma cell-adhesion molecule (Mel-CAM) led to strong antibody responses in mice, especially when these mimotopes were coupled with tetanus toxoid, indicating their potential as effective components of tumor vaccines.

The study demonstrated that both coupled and uncoupled mimotopes could stimulate T cell responses, with coupled mimotopes promoting a balanced Th1 and Th2 cytokine response, while uncoupled mimotopes favored a Th1 response, suggesting they can effectively induce both humoral and cellular immunity against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epitope-specific antibody response to Mel-CAM induced by mimotope immunization. Hafner, C., Wagner, S., Jasinska, J., et al.[2006]

References

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

Vaccines for melanoma. [2019]

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

Increased survival of patients treated with a vaccinia melanoma oncolysate vaccine: second interim analysis of data from a phase III, multi-institutional trial. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

Synthetic antitumor vaccines containing MUC1 glycopeptides with two immunodominant domains-induction of a strong immune response against breast tumor tissues. [2012]

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

Limited induction of tumor cross-reactive T cells without a measurable clinical benefit in early melanoma patients vaccinated with human leukocyte antigen class I-modified peptides. [2020]

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

A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Phase I/II clinical trial of a helper peptide vaccine plus PD-1 blockade in PD-1 antibody-naïve and PD-1 antibody-experienced patients with melanoma (MEL64). [2022]

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

The Use of Oncept Melanoma Vaccine in Veterinary Patients: A Review of the Literature. [2022]

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

Feasibility study of active immunotherapy in patients with solid tumors. [2019]

9. 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]

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

Melanoma vaccines. [2007]

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

Epitope-specific antibody response to Mel-CAM induced by mimotope immunization. [2006]