Vaccines for Advanced Melanoma

(TdVax Trial)

Overseen By Carol Ann Wiggs, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Duke University

Must be taking: PD-1 therapy

Must not be taking: Chronic steroids

Disqualifiers: Pregnancy, HIV, Hepatitis B, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4-5 months

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding a Tetanus Diphtheria (Td) or Polio Boost Immunization (IPOL) vaccine can be safely combined with standard immune checkpoint inhibitor therapy for advanced melanoma. Researchers aim to determine if these vaccines are safe and feasible alongside treatment for melanoma that has spread. Participants will receive their assigned vaccine during the fourth cycle of their ongoing cancer therapy. Those with confirmed advanced melanoma, who have not yet received systemic treatment and are scheduled to start certain immune therapies, may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

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.

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

Research shows that both the Polio Boost Immunization and the Tetanus Diphtheria Vaccine are very safe. Polio vaccines, like the one used in this study, rank among the safest available, with no serious side effects reported. They have successfully prevented polio for many years and are well-tolerated.

Similarly, the Tetanus Diphtheria Vaccine is considered safe. It is commonly used and usually only causes mild side effects, such as a sore arm at the injection site. It has proven effective in preventing infections and is a regular part of vaccination programs.

Both vaccines have a long history and strong scientific support for their safety. This study is a Phase 1 trial, specifically designed to assess the vaccines' safety in people, with significant attention given to how well participants handle the vaccines. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for advanced melanoma because they use vaccines typically associated with infectious diseases to potentially boost the immune response against cancer. The IPOL vaccine, a polio booster, and the Td vaccine, for tetanus and diphtheria, are being administered directly in proximity to tumors. This novel approach leverages the body's immune system in a unique way, potentially enhancing the effectiveness of existing immunotherapy. Unlike standard melanoma treatments, which often involve targeted therapies or checkpoint inhibitors, these vaccines could offer a new mechanism to stimulate the immune system to fight cancer cells more robustly.

What evidence suggests that these vaccines could be effective for advanced melanoma?

In this trial, participants will receive either the Polio Boost Immunization (IPOL) or the Tetanus Diphtheria (Td) vaccine. Research has shown that the IPOL vaccine can enhance the body's defenses in areas like the intestines, which is crucial for fighting infections. Specifically, studies demonstrated that IPOL increased intestinal immunity in children who had received the oral polio vaccine. Meanwhile, the Td vaccine is known to be safe and effective in preventing tetanus and diphtheria, and it has strongly activated the body's immune response. Both vaccines aim to strengthen the immune system, potentially helping the body fight cancer more effectively when used with treatments called immune checkpoint inhibitors. ^{2 6 7 8 9}

Who Is on the Research Team?

Georgia Beasley, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

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

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.

I am scheduled to receive PD-1 or PD-1 plus CTLA-4 therapy.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Polio Boost Immunization
• Tetanus Diptheria 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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1.

withpower.com

withpower.com/trial/phase-1-melanoma-8-2021-2df04

Vaccines for Advanced Melanoma (TdVax 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) ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10974833/

Inactivated Poliovirus Vaccine: Recent Developments and the ...

Two landmark studies in India demonstrated that IPV could boost intestinal mucosal immunity in OPV-vaccinated children, across age groups from 6 ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2211383525003764

Blades and barriers: Oral vaccines for conquering cancers ...

The above results showed that tumor growth was significantly retarded, and the survival time was prolonged in mice vaccinated with the BMCH-AH1-A5 vaccine via ...

4.

trials.braintumor.org

trials.braintumor.org/trials/NCT05077137

A Feasibility Study Utilizing Immune Recall to Increase ...

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 ...

5.

cancer.gov

cancer.gov/research/participate/clinical-trials/intervention/inactivated-poliovirus-vaccine?pn=1

Clinical Trials Using Inactivated Poliovirus Vaccine - NCI

NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying inactivated poliovirus vaccine.

6.

cdc.gov

cdc.gov/vaccine-safety/vaccines/polio.html

Polio Vaccine Safety

Polio vaccines have a favorable safety profile – the body of scientific evidence overwhelmingly supports their safety.

7.

fda.gov

fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert-IPOL.pdf

Package Insert - IPOL

Poliovirus Vaccine Inactivated induces the production of neutralizing antibodies against each type of virus which are related to protective efficacy. Antibody ...

8.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK221112/

Immunization Safety Review: SV40 Contamination of Polio ...

The committee examines the hypothesis that exposure to polio vaccine contaminated with simian virus 40 (SV40) can cause certain types of cancer.

9.

polioeradication.org

polioeradication.org/about-polio/the-vaccines/ipv/

Inactivated poliovirus vaccine - GPEI

Safety. IPV is one of the safest vaccines in use. No serious systemic adverse reactions have been shown to follow vaccination. More on vaccine safety.