What side effects are associated with this type of intervention?

Common side effects of treatments similar to Tri-Ad5 and N-803, which involve stimulating the immune system to target cancer cells, can include injection site reactions, fever, fatigue, and flu-like symptoms. More specific immune-related adverse effects may include autoimmune reactions, such as thyroiditis, and other inflammatory conditions. These treatments aim to enhance the body's immune response, which can sometimes lead to overactivation of the immune system, resulting in these side effects.

What prior FDA approvals exist?

Currently, there are no specific FDA-approved vaccines or immune enhancers for the treatment of Lynch Syndrome that directly match the mechanisms of Tri-Ad5 and N-803. However, immunotherapy approaches, including vaccines that stimulate the immune system to target cancer cells and immune enhancers, are being actively researched. These investigational treatments aim to leverage the body's immune response to prevent or treat cancers associated with Lynch Syndrome.

What other types of research exist?

Promising alternatives for Lynch Syndrome patients include pembrolizumab, an immune checkpoint inhibitor approved for MSI-H or MMR-deficient tumors, and personalized cancer vaccines targeting neoantigens specific to the patient's tumor profile. Additionally, adoptive cell transfer therapies, such as TIL (tumor-infiltrating lymphocytes) therapy, are emerging as potential options.

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Cancer Vaccine

Cancer Vaccines for Lynch Syndrome

Q: What is the mechanism of action of this treatment?

Lynch Syndrome treatments often focus on immunotherapy to harness the body's immune system against cancer cells. The Tri-Ad5 vaccine introduces substances from precancerous and cancerous cells to stimulate an immune response, teaching the immune system to target these cells. N-803 enhances this effect by boosting the immune response to the vaccine. This approach aims to provide a strong defense against cancer development in Lynch Syndrome patients, potentially lowering their cancer risk.

Phase 2

Recruiting

Led By Ajay Bansal

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

Participants must be >= 18 years old

Must not have

History of organ allograft or other history of immunodeficiency

Known HIV with CD4 count < 540, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at baseline, 52 weeks, and 104 weeks

Summary

This trial tests a vaccine and an immune booster to prevent cancer in people with Lynch syndrome. The vaccine teaches the body to fight cancer, and the booster makes this process stronger. Vaccines have shown robust potential for preventing Lynch syndrome cancers.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include typical reactions from vaccinations such as soreness at injection site or fever. Since it involves stimulating the immune system there's also a risk of autoimmune responses or allergic reactions especially for those with a history related to similar vaccines.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am mostly active and can care for myself.

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I am 18 years old or older.

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I have a genetic condition linked to colon cancer and a history of colon issues.

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I still have part of my lower colon or rectum.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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I have a history of blood clots that haven't been treated.

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I haven't taken steroids or immunosuppressants in the last 3 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at baseline, 52 weeks, and 104 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at baseline, 52 weeks, and 104 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and at baseline, 52 weeks, and 104 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Cumulative incidence rate of the composite endpoint of adenomas (tubular, tubulovillous and serrated), advanced adenomas and colon cancer

Secondary study objectives

Association of clinical factors with immune responses

Incidence of extracolonic neoplasms

Other study objectives

Differential expression analyses

Immune cell gene enrichment analysis

Number of antigen-specific T-cells, peripheral blood mononuclear cells (PBMCs), serum soluble factors and antibody levels

+1 more

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: Safety phase II (Tri-Ad5 , N-803)Experimental Treatment6 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 Treatment5 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 Treatment6 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 Group5 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2020

Biopsy

2014

Completed Phase 4

~1090

Colonoscopy

2012

Completed Phase 3

~115560

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Lynch Syndrome treatments often focus on immunotherapy to harness the body's immune system against cancer cells. The Tri-Ad5 vaccine introduces substances from precancerous and cancerous cells to stimulate an immune response, teaching the immune system to target these cells. N-803 enhances this effect by boosting the immune response to the vaccine. This approach aims to provide a strong defense against cancer development in Lynch Syndrome patients, potentially lowering their cancer risk.

Immunotherapy in Pancreatic Cancer: Why Do We Keep Failing? A Focus on Tumor Immune Microenvironment, Predictive Biomarkers and Treatment Outcomes.Advances in Immunotherapies for Gliomas.Efficacy of the NCCV Cocktail-1 vaccine for refractory pediatric solid tumors: A phase I clinical trial.