Cancer Vaccines for Lynch Syndrome

Not currently recruiting at 18 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Immunosuppressants, others

Disqualifiers: Immunodeficiency, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 12

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine, Tri-Ad5 (Adenovirus 5 CEA/MUC1/Brachyury Vaccine), combined with an immune-boosting treatment, N-803 (Nogapendekin Alfa), to determine its effectiveness in preventing colon and other cancers in individuals with Lynch syndrome. Lynch syndrome is a genetic condition that increases the risk of certain cancers. The trial aims to assess whether these injections can train the immune system to recognize and destroy cancer cells before they become problematic. Individuals who have experienced at least one issue, such as colon polyps or cancer related to Lynch syndrome, but have been cancer-free for 6 months, might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer prevention.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on certain immunosuppressive drugs or other investigational agents. It's best to discuss your specific medications with the study team.

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

Research has shown that the Tri-Ad5 vaccine, which targets specific proteins in cancer cells, was tested in earlier studies. Participants generally tolerated the vaccine well, with no major safety concerns reported.

For N-803, more information is available since the FDA has already approved it for bladder cancer that doesn't respond to other treatments. In those cases, fewer than 15% of patients experienced side effects such as tiredness, mild nausea, or slight bladder irritation. These side effects are uncommon and mostly mild.

Overall, both treatments have demonstrated a good safety record in previous studies and uses, with no serious safety issues commonly reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Tri-Ad5 vaccine for Lynch Syndrome because it uses a novel approach to cancer prevention by stimulating the immune system with adenovirus-based vaccines targeting CEA, MUC1, and Brachyury proteins. This method aims to train the body to recognize and fight cancer cells more effectively, potentially reducing the risk of cancer development in Lynch Syndrome patients. Additionally, the combination with N-803, an immune-stimulating agent, may further enhance the immune response, offering a more proactive strategy compared to current options like regular surveillance and surgery. This innovative approach could provide a non-invasive alternative that empowers the immune system to prevent cancer before it starts.

What evidence suggests that this trial's treatments could be effective for Lynch syndrome?

Research shows that the Tri-Ad5 vaccine, a treatment in this trial, targets three proteins commonly found in cancer cells: CEA, MUC1, and brachyury. This vaccine has shown promise in helping the immune system attack these cancer-related proteins. Early studies have demonstrated that this method can create strong immune responses against tumor cells.

Additionally, N-803, also known as Anktiva, is another treatment option in this trial that enhances the immune system's ability to fight cancer. It has shown promising results in various types of cancer, including positive outcomes when combined with other treatments. In this trial, some participants will receive both Tri-Ad5 and N-803, which could potentially reduce the risk of developing cancer in people with Lynch syndrome by boosting the body's natural defenses. ^{1 3 4 5 6}

Who Is on the Research Team?

Ajay Bansal

Principal Investigator

University of Kansas

Are You a Good Fit for This Trial?

This trial is for adults with Lynch syndrome who've had adenomas, advanced adenomas, or colon cancer. They must be at least 6 months post any cancer treatment and have part of their colon/rectum intact. Participants need normal blood counts and organ function tests, agree to contraception use, and space out COVID vaccines around the study timeline. Exclusions include untreated blood clots, recent immunosuppressants use, certain infections like HIV/HBV/HCV with specific conditions, pregnancy/breastfeeding women, history of severe vaccine allergies.

Inclusion Criteria

Your creatinine levels are within the normal range set by the hospital.

You have a white blood cell count of at least 3,000 per microliter.

It has been over 6 months since my last cancer treatment.

Exclusion Criteria

I have had an organ transplant or have a condition that weakens my immune system.

I have HIV with a CD4 count under 540, or I have hepatitis B or C.

Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Phase I

Participants receive Tri-Ad5 subcutaneously at weeks 0, 4, 8, and 52. Participants also undergo standard of care colonoscopy with biopsy at baseline, at 52 weeks and 104 weeks.

104 weeks

4 visits (in-person) for vaccination, 3 visits (in-person) for colonoscopy

Safety Phase II

Participants receive Tri-Ad5 and N-803 subcutaneously at weeks 0, 4, 8, and 52. Participants also undergo standard of care colonoscopy with biopsy at baseline, 52 weeks and 104 weeks.

104 weeks

4 visits (in-person) for vaccination, 3 visits (in-person) for colonoscopy

Randomized Control Phase

Participants are randomized into two arms: Arm I receives Tri-Ad5 and N-803, Arm II receives placebo. Both arms undergo standard of care colonoscopy with biopsy at baseline, 52 weeks, and 104 weeks.

104 weeks

4 visits (in-person) for vaccination, 3 visits (in-person) for colonoscopy

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5
• Nogapendekin Alfa
• Placebo Administration

Trial Overview The trial is testing a combination of Tri-Ad5 vaccine (with three substances targeting precancer/cancer cells) and N-803 (an immune enhancer), aiming to prevent cancers in those with Lynch syndrome. The idea is that this combo might train the immune system to fight off potential cancer cells more effectively.

How Is the Trial Designed?

Group I: Safety phase II (Tri-Ad5 , N-803) Experimental Treatment 6 Interventions

Participants receive Tri-Ad5 SC and N-803 SC at weeks 0, 4, 8, and 52. Participants also undergo SOC colonoscopy with biopsy at baseline and at 52 weeks and 104 weeks. Participants undergo blood sample collection throughout the study.

Group II: Safety phase I (Tri-Ad5) Experimental Treatment 5 Interventions

Participants receive Tri-Ad5 SC at weeks 0, 4, 8, and 52. Participants also undergo SOC colonoscopy with biopsy at baseline and at 52 weeks and 104 weeks. Participants undergo blood sample collection throughout the study.

Group III: Arm I (Tri-Ad5, N-803) Experimental Treatment 6 Interventions

Participants receive Tri-Ad5 SC and N-803 SC at weeks 0, 4, 8, and 52. Participants also undergo SOC colonoscopy with biopsy at baseline and at 52 and 104 weeks. Participants undergo blood sample collection throughout the study.

Group IV: Arm II (placebo) Placebo Group 5 Interventions

Participants receive placebo SC at weeks 0, 4, 8, and 52. Participants also undergo SOC colonoscopy with biopsy at baseline and at 52 and 104 weeks. Participants undergo blood sample collection throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The study developed a dendritic cell-based vaccine targeting the tumor-associated antigen MUC4, which is overexpressed in various cancers, showing promise for broad applicability in cancer immunotherapy.

In vitro tests demonstrated that the vaccine effectively primed lymphocytes to generate strong cytotoxic responses against MUC4-expressing cells, indicating its potential efficacy in treating MUC4-associated tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cells expressing a combined PADRE/MUC4-derived polyepitope DNA vaccine induce multiple cytotoxic T-cell responses. Wei, J., Gao, W., Wu, J., et al.[2019]

The GI-6301 vaccine, which targets the brachyury protein, was shown to be safe and capable of activating T-cell immune responses in most patients, even those who had undergone extensive prior treatments, in a phase I trial with 34 participants.

Two patients with chordoma experienced disease control, and one colorectal cancer patient showed stable disease for over a year, indicating potential clinical activity of the vaccine and supporting further investigation in phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of a Yeast-Based Therapeutic Cancer Vaccine (GI-6301) Targeting the Transcription Factor Brachyury. Heery, CR., Singh, BH., Rauckhorst, M., et al.[2022]

The Ad5 PSA/MUC-1/brachyury vaccine targeting metastatic castration-resistant prostate cancer (mCRPC) was found to be safe and well-tolerated, with no severe treatment-related adverse events reported in a trial involving 18 patients.

The vaccine demonstrated clinical activity, with one patient achieving a partial response and five showing a decline in PSA levels, indicating potential effectiveness in generating an immune response against tumor-associated antigens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of a multitargeted recombinant Ad5 PSA/MUC-1/brachyury-based immunotherapy vaccine in patients with metastatic castration-resistant prostate cancer (mCRPC). Bilusic, M., McMahon, S., Madan, RA., et al.[2021]

The study demonstrates that MUC1 is essential for the effectiveness of colorectal cancer stem cell (CCSC) vaccines, as MUC1 knockdown reduced the vaccine's anti-tumor efficacy, while MUC1 overexpression enhanced it.

CCSC vaccines significantly reduced tumor growth by targeting CCSCs, increasing the activity of immune cells like NK cells, and promoting the release of key immune factors, indicating a robust immune response against colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colorectal cancer stem cell vaccine with high expression of MUC1 serves as a novel prophylactic vaccine for colorectal cancer. Guo, M., Luo, B., Pan, M., et al.[2021]

The DNA electroporation and adenovirus-based genetic vaccine effectively triggered an immune response against the human carcinoembryonic antigen (CEA) in mouse models of colorectal cancer, demonstrating significant antitumor effects.

This study suggests that targeting CEA with genetic vaccines could be a promising strategy for treating gut tumors, as the models used closely mimic human colorectal cancer, allowing for better evaluation of vaccine efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A therapeutic cancer vaccine targeting carcinoembryonic antigen in intestinal carcinomas. Mori, F., Giannetti, P., Peruzzi, D., et al.[2010]

The MVA-brachyury-TRICOM vaccine, designed to target the brachyury transcription factor associated with cancer progression, was safely administered to 38 advanced cancer patients without any dose-limiting toxicities, indicating a favorable safety profile.

The vaccine successfully activated brachyury-specific T-cell responses in most patients, suggesting its potential efficacy in enhancing the immune response against tumors that express brachyury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of a Poxviral TRICOM-Based Vaccine Directed Against the Transcription Factor Brachyury. Heery, CR., Palena, C., McMahon, S., et al.[2019]

The novel adenovirus vector platform (Ad5 [E1-, E2b-]) shows promise in reducing immune response to the vector itself, allowing for more effective delivery of tumor-associated antigens (TAAs) like CEA, brachyury, and MUC1 in cancer vaccines.

The combination vaccine (Tri-Ad5) targeting multiple TAAs demonstrated the ability to activate specific T cell responses without significant competition between the antigens, suggesting it could be an effective approach for treating diverse human tumors in future clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic. Gabitzsch, ES., Tsang, KY., Palena, C., et al.[2018]

The latest generation of high-capacity adenoviral vectors has a significantly improved safety profile compared to earlier versions, as they are devoid of viral genes that cause inflammatory responses and toxicity, leading to more prolonged therapeutic gene expression.

Despite their advancements, high-capacity adenoviral vectors can still cause transient toxic effects, and while there is a low risk of malignancy associated with these vectors, integrating adenoviral vectors pose a higher risk due to their random integration into target genomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biosafety of adenoviral vectors. Chuah, MK., Collen, D., VandenDriessche, T.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05419011

Testing a Combination of Vaccines for Cancer Prevention ... This phase IIb trial tests whether Tri-Ad5 in combination with N-803 works to prevent colon and other cancers in participants with Lynch syndrome.

2. immunitybio.com immunitybio.com/immunitybio-announces-full-accrual-of-first-two-phases-of-cancer-vaccine-trial-in-participants-with-lynch-syndrome-and-initiation-of-randomized-controlled-phase-of-the-trial/

ImmunityBio Announces Full Accrual of First Two Phases ... ImmunityBio's Tri-Ad5 vaccines target three tumor-associated antigens: brachyury, carcinoembryonic antigen (CEA), and mucin-1 (MUC1).

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/adenovirus-5-cea-muc1-brachyury-vaccine-tri-ad5?pn=1

Clinical Trials Using Adenovirus 5 CEA/MUC1/Brachyury ... NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying adenovirus 5 cea/muc1/brachyury vaccine ...

4. dana-farber.org dana-farber.org/clinical-trials/23-039

A Phase IIb Clinical Trial of the Multitargeted Recombinant ... This phase IIb trial tests whether Tri-Ad5 in combination with N-803 works to prevent colon and other cancers in participants with Lynch syndrome.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31594913/

Based Immunotherapy Vaccine Regimen in Patients with ... A novel adenovirus-based vaccine targeting three human tumor-associated antigens-CEA, MUC1, and brachyury-has demonstrated antitumor cytolytic T-cell responses.

6. immunitybio.com immunitybio.com/national-multicenter-trial-opens-to-study-immunitybios-tri-ad5-cancer-vaccines-plus-n-803-to-prevent-cancer-in-people-with-lynch-syndrome/

Colorectal Cancer Vaccine Trial Opens to Test Tri-Ad5 Plus ... National Multicenter Trial Opens to Study ImmunityBio's Tri-Ad5 Cancer Vaccines Plus N-803 to Prevent Cancer in People with Lynch Syndrome.