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Testing a combination of vaccines to prevent cancer in Lynch syndrome patients

A Phase IIB Clinical Trial of the Multitargeted Recombinant Adenovirus 5 (CEA/MUC1/Brachyury) Vaccines (TRI-AD5) and IL-15 Superagonist N-803 in Lynch Syndrome

Phase 2 Interventional National Cancer Institute (NCI) · NCT05419011

This study is testing a combination of vaccines to see if they can help prevent cancer in people with Lynch syndrome.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment186 (estimated)
Ages18 Years and up
SexAll
SponsorNational Cancer Institute (NCI) NIH
Drugs / interventionschemotherapy, immunotherapy, radiation, prednisone
Locations16 sites (Phoenix, Arizona and 15 other locations)
Trial IDNCT05419011 on ClinicalTrials.gov

What this trial studies

This phase IIb trial evaluates the effectiveness of a combination of Tri-Ad5 vaccines and N-803 in preventing colorectal and other cancers in individuals with Lynch syndrome. The Tri-Ad5 vaccine contains substances that target precancerous and cancerous cells, aiming to stimulate the immune system to recognize and destroy these cells. The study also assesses the safety and tolerability of this combination, as well as its impact on immune responses and quality of life for participants. Additionally, it explores correlations between clinical factors and immune responses.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with Lynch syndrome and a history of colorectal neoplasms or cancer.

Not a fit: Patients with active cancer or those who do not meet the genetic criteria for Lynch syndrome may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the incidence of colorectal and other cancers in patients with Lynch syndrome.

How similar studies have performed: Other studies have shown promise in using vaccine-based approaches for cancer prevention, but this specific combination is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Participants with LS defined as one of the following:

  * Mutation positive: MLH1, MSH2/EPCAM and MSH6 genotypes with prior history of ≥1 colorectal neoplasms\*\* (tubular or tubulovillous adenoma\[s\] or sessile serrated polyps/adenomas/lesion\[s\] or traditional serrated adenoma\[s\]), and/or colorectal cancer\[s\] (but no active cancer for 6 months) OR
  * PMS2 genotype with prior history of colon cancer(s) (but no active cancer for 6 months)

    * Note: Should be confirmed by pathology report or letter from endoscopist to participant
* Participants must have at least part of the descending/sigmoid colon and/or rectum intact
* Participants must be at least 6 months from any cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy or radiation). Ongoing adjuvant endocrine therapy is allowed
* Participants \>= 18 years will be enrolled. Because the risk of LS related cancers is very low in participants \< 18 years of age, children and adolescents are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
* Leukocytes \>= 3,000/microliter
* Absolute neutrophil count \>= 1,500/microliter
* Platelets \>= 100,000/microliter
* Total bilirubin =\< institutional upper limit of normal

  * Note: Higher bilirubin levels (\<= 3 mg/dL) can be allowed if due to a known benign liver condition, i.e. Gilbert's
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x institutional upper limit of normal
* Creatinine =\< institutional upper limit of normal or estimated glomerular filtration rate (eGFR) \>= 60 ml/min/1.73m\^2
* The effects of the Tri-Ad5 vaccines and N-803 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
* Ability to understand and the willingness to sign a written informed consent document
* Participants must be willing and able to space coronavirus disease (COVID) vaccines at least 2 weeks prior to and 2 weeks after receipt of study agent

Exclusion Criteria:

* History of organ allograft or other history of immunodeficiency
* Known human immunodeficiency virus (HIV) with CD4 count \< 540, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Subjects with laboratory evidence of cleared HBV and HCV infection will be permitted. Poorly controlled HIV may prevent an adequate immune response to the vaccine and will be an exclusion criterion
* Subjects requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 3 months of vaccination
* Participants may not be receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to adenovirus-based vaccines and N-803
* Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because of the unknown effects of the vaccine and N-803 on the fetus. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with the vaccine plus N-803, breastfeeding should be discontinued if the mother is treated with the vaccine plus N-803
* History of untreated thrombotic disorders
* Participants who experienced severe side effects or allergic reactions to previous adenovirus-based vaccines (such as Johnson and Johnson COVID vaccine) will be excluded
* History of atrial fibrillation

Where this trial is running

Phoenix, Arizona and 15 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Colorectal CarcinomaColorectal NeoplasmLynch Syndrome
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.