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Colorectal CarcinomaPhase 2NCT05419011

Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome

A Phase 2 study testing Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5, Biopsy Procedure and Biospecimen Collection in people with Colorectal Carcinoma and Colorectal Neoplasm, run by National Cancer Institute (NCI) at 14 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Each of the three injections in Tri-Ad5 vaccine contain a different substance that is in precancer and cancer cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5, Biopsy Procedure and Biospecimen Collection
Type of treatment
Vaccines, Surgery or procedure
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
186 participants
Where
14 sitesin 2 countries
Study dates
8 May 2023to 1 Jan 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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
  • History of gastrointestinal hemorrhage and intracranial hemorrhage

Trial locations and contacts

14 sites in 2 countries.

14 sites in 2 countries

United States13 sites

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Northwestern University

    Chicago, Illinois, 60611

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • UCSF Medical Center-Parnassus

    San Francisco, California, 94143

  • University of Arizona Cancer Center - Prevention Research Clinic

    Tucson, Arizona, 85719

Other trials in United States

Puerto Rico1 site

  • University of Puerto Rico

    San Juan, 00936

Other trials in Puerto Rico

About this study

Official title: 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

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. Each of the three injections in Tri-Ad5 vaccine contain a different substance that is in precancer and cancer cells. Injecting these substances may cause the immune system to develop a defense against cancer that recognizes and destroys any precancer and cancer cells that produce these proteins in the future. N-803 may increase immune responses to other vaccines. Giving Tri-Ad5 in combination with immune enhancing N-803 may lower the chance of developing colon and other cancers in participants with Lynch syndrome.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate if the combination of trivalent adenovirus-5 (Tri-Ad5) vaccines and IL-15 superagonist nogapendekin alfa inbakicept (N-803) reduces the incidence of colorectal neoplasms in patients with Lynch syndrome (LS).

SECONDARY OBJECTIVES:

  1. To evaluate the safety and tolerability of the Tri-Ad5 vaccines + N-803 in combination.

II. To correlate clinical factors such as use of aspirin and non-steroidal anti-inflammatory drugs (NSAID), smoking and alcohol intake with immune responses.

III. To evaluate the effect of Tri-Ad5 vaccines on the incidence of LS-related extracolonic cancers.

IV. To systematically measure the participants' behavior and experience in terms of vaccine uptake, cancer-specific distress and quality of life.

EXPLORATORY OBJECTIVES:

  1. To determine the ability of the Tri-Ad5 vaccines + N-803 to generate a 2-fold increase in T cell responses (cell-mediated immunity) at week 12 (early immune response) and at week 56 (long-term memory response).

II. To evaluate circulating anti-MUC1 IgG (antibody-mediated immunity) after Tri-Ad5 vaccines + N-803.

III. To compare the expression of the three tumor associated antigen (TAAs): MUC1, carcinoembryonic antigen (CEA) and brachyury in colorectal neoplasms before and after Tri-Ad5 vaccines + N-803.

IV. To evaluate changes in the immune profile and abundance of resident immune cell types in colonic mucosa after vaccination with Tri-Ad5 vaccines + N-803 using messenger ribonucleic acid sequencing (mRNAseq) and immunohistochemistry (IHC).

  1. To test the effects of the vaccines alone or in combination with N-803 on specific immune subsets of peripheral blood mononuclear cells (PBMCs) and serum soluble factors and cytokines.

VI. To compare the expression of stem cell markers in colorectal neoplasms before and after Tri-Ad5 vaccines + N-803.

VII. To compare the number of mismatch repair deficient (MMR-deficient) crypts at baseline to the number of MMR-deficient crypts at the one year post-vaccination colonoscopy both overall and on a per patient basis.

OUTLINE:

SAFETY PHASE I: Participants receive Tri-Ad5 subcutaneously (SC) at weeks 0, 4, 8, and 52. Participants also undergo standard of care (SOC) colonoscopy with biopsy at baseline, at 52 weeks and 104 weeks.

SAFETY PHASE II: 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, 52 weeks and 104 weeks.

RANDOMIZED CONTROL PHASE: Participants are randomized into 1 of two arms.

ARM I: 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.

ARM II: 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.

Being tested
Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5, Biopsy Procedure, Biospecimen Collection, Colonoscopy, Nogapendekin Alfa
Medical subject headings
Colorectal Neoplasms, Colorectal Neoplasms, Hereditary Nonpolyposis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5Biological

    Also called Ad5 CEA/MUC1/Brachyury Vaccine Tri-Ad5, Ad5-CEA/Ad5-MUC1/Ad5-Brachyury Vaccine Tri-Ad5, Adenoviral CEA/MUC1/Brachyury Vaccine Tri-Ad5, Tri Ad5

    Given SC

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • ColonoscopyProcedure or surgery

    Undergo SOC colonoscopy

  • Nogapendekin AlfaDrug

    Given nogapendekin alfa inbakicept (N-803) SC

  • Placebo AdministrationDrug

    Given SC

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT05419011
Study groupRoleWhat they receive
Arm I (Tri-Ad5, N-803)ExperimentalParticipants 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.
Receives: Biological: Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Colonoscopy; Drug: Nogapendekin Alfa; Other: Questionnaire Administration
Arm II (placebo)Placebo comparatorParticipants 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.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Colonoscopy; Drug: Placebo Administration; Other: Questionnaire Administration
Safety phase I (Tri-Ad5)ExperimentalParticipants 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.
Receives: Biological: Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Colonoscopy; Other: Questionnaire Administration
Safety phase II (Tri-Ad5 , N-803)ExperimentalParticipants 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.
Receives: Biological: Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Colonoscopy; Drug: Nogapendekin Alfa; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Will be compared between the two arms using a stratified Cochran-Mantel-Haenszel test where the randomization stratification factors will be included as strata. The cumulative events rates will be reported for each study arm along with the corresponding two-sided 95% confidence intervals.

    Measured: At 104 weeks

Secondary outcomes (4)

  1. Incidence of adverse events

    Identify the adverse events using Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 104 weeks

  2. Association of clinical factors with immune responses

    Will be evaluated by conducting univariate and multivariate binary regression analyses. These analyses will be conducted for both arms combined (in which case arm is included as a stratification factor in the model) and each arm separately. The proportions of cells within adenomas expressing stem cells markers pre- and post-vaccination will be compared within each study arm using the signed rank test, and within-subject changes will be compared between responders and non-responders using Wilcoxon rank-sum test for each arm separately and both arms combined. Comparisons between study arms will be conducted using a Wilcoxon rank-sum test.

    Measured: At 104 weeks

  3. Incidence of extracolonic neoplasms

    Will compare the observed incidences of lynch syndrome (LS)-related extracolonic cancers to historical control incidence of LS-related extracolonic cancers in this patient population. We will collect the information about extracolonic cancers by asking the participants and by reviewing the pathology reports for confirmation.

    Measured: At 104 weeks

  4. Participants' behavior and experience

    Descriptive statistics will be used to summarize the results.

    Measured: At baseline, 12 weeks and 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2022
  2. Study start8 May 2023
  3. Primary completion1 Jul 2027 (estimated)
  4. Study completion1 Jan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
186 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05419011
Sponsor's protocol ID
NCI-2021-14234
Other IDs
NCI-2021-14234, NCI 21-05-01, NCI21-05-01, INT21-05-01, P30CA060553, UG1CA242596, UG1CA242609, UG1CA242632
Status last verified
May 2026
First submitted
14 Jun 2022
Last updated
17 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 'NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page'

Publications

  • Bansal A, Stoffel EM, Lim R, Stanich PP, Patel SG, Burke CA, Hall MJ, Singh A, Boardman LA, Samadder NJ, Ballestar V, Muller C, Scott AJ, Benante KA, Xu Y, Eickhoff J, Hyun M, Zaborek J, Aquila L, Umar A, Szabo E, Della'Zanna G, Richmond E, Bengtson L, Schlom J, Donahue RN, Toney NJ, Horn LA, Palena C, Gulley JL, Samaddar S, Moore DF Jr, Sharma P, Madan R, Hurley KE, Soon-Shiong P, Gabitzsch E, Sender L, Brenner D, Schuetze S, Djuric Z, Barroilhet LM, Thompson P, Bauman J, Khan SA, Vilar E. Design and preliminary report of a randomized phase IIb clinical trial of multitargeted recombinant adenovirus 5 vaccines against CEA, MUC1, and brachyury (Tri-Ad5) and the IL-15 receptor superagonist nogapendekin alfa inbakicept in Lynch syndrome (TRIAD5-Plus): the first cross-network trial of the Cancer Prevention Clinical Trials Network (CP-CTNet). Front Immunol. 2026 May 19;17:1809281. doi: 10.3389/fimmu.2026.1809281. eCollection 2026.

    PubMed 42238576

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5, Biopsy Procedure and Biospecimen Collection in people with Colorectal Carcinoma and Colorectal Neoplasm, run by National Cancer Institute (NCI) at 14 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cumulative incidence rate of the composite endpoint of adenomas (tubular, tubulovillous and serrated), advanced adenomas and colon cancer (time frame: At 104 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05419011, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026; AzTrials last refreshed its copy on 7 Nov 2026.

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