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Colorectal CarcinomaPhase 1/2NCT05078866

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients

A Phase 1/2 study testing Adenoviral Tumor-specific Neoantigen Priming Vaccine GAd-209-FSP, Biospecimen Collection and Endoscopic Biopsy in people with Colorectal Carcinoma and Lynch Syndrome, run by National Cancer Institute (NCI) at 4 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 Ib/II trial evaluates the safety and effect of the Nous-209 vaccine in Lynch syndrome patients. Lynch syndrome is an inherited disorder in which affected individuals have a higher-than-normal chance of developing colorectal cancer and certain other types of cancer, often before the age of 50. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Carcinoma, Lynch Syndrome
What is being tested?
Adenoviral Tumor-specific Neoantigen Priming Vaccine GAd-209-FSP, Biospecimen Collection and Endoscopic Biopsy
Type of treatment
Vaccines, Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
4 sitesin 2 countries
Study dates
10 Nov 2022to 30 Sep 2026
Phase
Phase 1/2
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 must have a clinical diagnosis of Lynch syndrome (LS) as defined by:
  • Mutation-positive LS: documented carriers (or obligate carriers by pedigree) of a germline mutation in MMR genes (MLH1, MSH2/EPCAM, MSH6, or PMS2) that is deleterious/pathogenic or suspected to be deleterious/pathogenic (known or predicted to be detrimental/loss of function, respectively). The mutation must have been identified through a Clinical Laboratory Improvement Act (CLIA)-approved laboratory setting or an equivalent international agency. Final determination of eligibility for any discordant results in pathogenicity of the mutation will be determined by the study investigator. A formal eligibility exception in those instances will not be required as long as approval by the overall study principal investigator (PI) has been granted and documented
  • Mutation-negative LS (also known as "Lynch-like syndrome" or "suspected Lynch syndrome): individuals with both of the following:
  • A personal history of a non-sporadic MMR-deficient premalignant lesion (i.e., colorectal polyp) or a non-sporadic MMR-deficient malignant tumor, where "non-sporadic MMR deficiency" is defined by (1) the loss of MLH1, MSH2, MSH6, or PMS2 expression by immunohistochemistry (IHC), or (2) the detection of MSI by PCR or both, but no evidence of MLH1 promoter methylation in cases with loss of both MLH1 and PMS2, All testing must have been performed in accordance with local institutional guidelines in a CLIA- approved setting. (Note: central confirmation of MMR expression status, MSI, MLH1 promoter methylation or BRAF mutation is not required.); and
  • Documented results of germline mutation testing performed in a CLIA-approved laboratory environment, demonstrating either a variant of unknown significance in MMR genes or the lack of a clinically significant variant in MMR genes; or, documentation that the individual declined to undergo germline MMR genetic testing
  • Participants must have no evidence of active or recurrent invasive cancer for 6 months prior to screening
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  • Participants must be at least 6 months from any prior cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy, hormonal therapy, or radiation)
  • Participants must have endoscopically accessible distal colon and/or rectal mucosa (i.e., participants must have at least part of the descending/sigmoid colon and/or rectum intact)
  • Participants must consent to standard of care surveillance with colonoscopy with biopsies every 12 months
  • Participants must consent to refrain from using aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase (COX) inhibitors for the duration of the trial, except for cardio-preventive aspirin (< 100 mg daily). Individuals taking such drugs may not be enrolled unless they are willing to stop the medications (and possibly change to alternative non-excluded medications to treat the same conditions) no less than 1 month prior to enrollment. Participants will discuss with their primary care provider/local provider about the discontinuation of such medication(s) and obtain approval prior to stopping any agent
  • Age >= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of Nous-209 in participants < 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Hemoglobin >= 10 g/dL or hematocrit >= 30 %
  • Leukocyte count >= 3,500/microliter
  • Platelet count >= 100,000/microliter
  • Absolute neutrophil count >= 1,500/microliter
  • Estimated glomerular filtration rate (eGFR) (or creatinine clearance calculated using the Cockcroft-Gault equation) ≥ 60 mL/min/1.73m^2 (mL/min, within institutional limits of normal)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2 times the institutional upper limit of normal (ULN)
  • Total bilirubin =< 1.5 the ULN; participants with Gilbert's disease may be enrolled with higher total bilirubin if their direct bilirubin is =< 1.5 times the ULN
  • Participants must consent to refrain from receiving any other type of vaccination during the first 10 weeks of the trial
  • Participants must consent to refrain from receiving adenoviral-based vaccines for the duration of the trial (including the period from week 9 to week 52)
  • Willing and able to adhere to the prohibitions and restrictions specified in the final approved protocol
  • The effects of Nous-209 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 for the duration of study participation (12 months) and 6 months after end of study. 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 (available for both English- and Spanish-speaking individuals)
  • Participants must have been confirmed eligible and met all study inclusion criteria for participation in study Cohort 1
  • Participants must have completed all baseline procedures and received a complete cycle of GAd20- 209 FSP (prime) and MVA-209-FSP (boost) vaccination per protocol for Cohort 1
  • Participants must have undergone collection of research blood samples at baseline (week 0) and week 9 for evaluation of the Nous-209-induced immunogenicity endpoint as specified for Cohort 1. Only participants with evaluable and proved immunogenicity response at Week 9 are eligible for participation in Cohort 2
  • Participants must consent to refrain from receiving any other type of vaccination during weeks 52 to 68 of the trial
  • Participants must consent to refrain from receiving adenoviral-based vaccines for the duration of the trial (including the period from week 52 to week 68)
  • Participants must consent to refrain from using aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase (COX) inhibitors for the duration of the cohort 2, except for cardiopreventive aspirin (< 100 mg daily). Individuals taking such drugs may not be enrolled unless they are willing to stop the medications (and possibly change to alternative non-excluded medications to treat the same conditions) no less than 1 month prior to enrollment. Participants will discuss with their primary care provider/local provider about the discontinuation of such medication(s) and obtain approval prior to stopping any agent
  • Female participant must agree to a pregnancy test at week 52

Who cannot join

  • Prior receipt of a recombinant adenoviral or MVA vaccine including COVID-19 adenovirus vaccines within the previous 6 months
  • Histologically-confirmed high-grade dysplasia or cancer on biopsy at screening
  • Individuals with active malignancy (excluding non-melanoma skin cancer)
  • Any serious uncontrolled and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures
  • Active infection (acute and self-limited) or human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Participants with laboratory evidence of cleared HBV and HCV infection will be permitted
  • History of organ allograft or other history of immunodeficiency
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  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients, or to egg proteins
  • Individuals with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications (such as infliximab, rituximab, adalimumab, tacrolimus) within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • Pregnant or breastfeeding or planning to become pregnant within 6 months after the end of study. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with Nous-209, breastfeeding should be discontinued if the mother is treated with Nous-209
  • Men attempting or planning to conceive children during the study or within 6 months after the end of the study
  • Participants may not be receiving any other investigational agents
  • Cohort 2 only: participants who experienced grade 3 or higher AEs attributed to study drug in Cohort 1, excluding reactogenicity events

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

United States3 sites

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

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 Ib/II Clinical Trial of Nous-209 for Recurrent Neoantigen Immunogenicity and Cancer Immune Interception in Lynch Syndrome

This phase Ib/II trial evaluates the safety and effect of the Nous-209 vaccine in Lynch syndrome patients. Lynch syndrome is an inherited disorder in which affected individuals have a higher-than-normal chance of developing colorectal cancer and certain other types of cancer, often before the age of 50. In Lynch syndrome, errors in the genetic information inside cells are not properly corrected. When that happens, the cells produce new proteins called neoantigens. Neoantigens are recognized by the body's immune system as foreign, and the body tries to get rid of them. Nous-209 is a vaccine made with man-made copies of some of those neoantigens. This trial aims to see whether the Nous-209 vaccine is safe to give to patients with Lynch syndrome, whether people are able to take the Nous-209 vaccine without becoming too uncomfortable, and how the immune system of patients with Lynch syndrome respond to the Nous-209 vaccine. This trial may help researchers determine whether receiving Nous-209 have an effect on the development of polyps or tumors in the colon.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety and tolerability of adenoviral tumor-specific neoantigen priming vaccine GAd-209-FSP (GAd20-209-FSPs) (1 prime) and MVA tumor-specific neoantigen boosting vaccine MVA-209-FSP (MVA-209-FSPs) (1 boost) vaccination when administered as a single agent (monotherapy) in participants with Lynch syndrome (LS).

II. To evaluate the neoantigen-specific immunogenicity of GAd20-209-FSPs (1 prime) and MVA-209-FSPs (1 boost) vaccination when administered as a single agent (monotherapy) in participants with LS.

III. To evaluate the neoantigen-specific immunogenicity of GAd20-209-FSP prime and MVA-209-FSP boost or MVA-209-FSP boost alone when administered to previously-vaccinated immunogenic participants with LS.

IV. To evaluate the safety and tolerability of GAd20-209-FSP prime and MVA-209-FSP boost or MVA-209-FSP boost alone when administered to previously vaccinated immunogenic participants with LS.

SECONDARY OBJECTIVES:

  1. To assess the effect of Nous-209 vaccination on T cell immune profile and T cell receptor (TCR) repertoire in the peripheral blood of participants with LS.

II. To assess the effect of Nous-209 vaccination on TCR repertoire within histologically normal colorectal mucosal of participants with LS.

III. To evaluate the effect of Nous-209 vaccination on tumor infiltrating lymphocyte (TIL) immune profile and TCR repertoire within colorectal adenomas in participants with LS.

IV. To assess the cytotoxicity of matched T cells on participant-derived colorectal adenoma organoids following Nous-209 vaccination in participants with LS.

  1. To evaluate the effect of Nous-209 vaccination on the burden of colorectal adenomas/advanced neoplasia/carcinoma in participants with LS.

VI. To assess the effect of Nous-209 vaccination on the burden of LS-related carcinomas in participants with LS.

VII. To evaluate the effect of Nous-209 vaccination on cell free deoxyribonucleic acid (DNA) (cfDNA) mutation profiles and cfDNA burden in participants with LS.

VIII. To correlate tobacco and alcohol consumption with the immune response to Nous-209 in trial participants.

IX. To assess the mismatch repair (MMR) and/or microsatellite instability (MSI) status of polyps (and adjacent normal mucosa as control) detected in the baseline and end-of-the-study colonoscopy using different technologies such as immunohistochemistry, MSI analysis by polymerase chain reaction (PCR), or next-generation sequencing.

OUTLINE:

PART I: Patients receive GAd20-209-FSPs intramuscularly (IM) on day 1 and MVA-209-FSPs IM at week 8. Patients undergo endoscopy with biopsy during screening and follow up as well as blood sample collection on the trial.

PART II: Eligible patients from Part I are randomized to 1 of 2 arms.

ARM A: Patients receive GAd20-209-FSPs IM at week 52 and MVA-209-FSPs IM at week 60. Patients undergo endoscopy with biopsy as well as blood sample collection on the trial.

ARM B: Patients receive MVA-209-FSPs IM at week 52. Patients undergo endoscopy with biopsy as well as blood sample collection on the trial.

After completion of study treatment, patients are followed up at weeks 16, 24, 36, and 52.

Being tested
Adenoviral Tumor-specific Neoantigen Priming Vaccine GAd-209-FSP, Biospecimen Collection, Endoscopic Biopsy, MVA Tumor-specific Neoantigen Boosting Vaccine MVA-209-FSP, Questionnaire Administration
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.

  • Adenoviral Tumor-specific Neoantigen Priming Vaccine GAd-209-FSPBiological

    Also called GAd-209-FSP, GAd20-209-FSP, Great Ape Adenoviral Tumor-specific Neoantigen Priming Vaccine GAd-209-FSP

    Given IM

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Endoscopic BiopsyProcedure or surgery

    Also called Endoscopy and Biopsy

    Undergo endoscopy with biopsy

  • MVA Tumor-specific Neoantigen Boosting Vaccine MVA-209-FSPBiological

    Also called Modified Vaccinia Ankara Tumor-specific Neoantigen Boosting Vaccine MVA-209-FSP, Modified Vaccinia Virus Ankara Tumor-specific Neoantigen Boosting Vaccine MVA-209-FSP, MVA-209-FSP

    Given IM

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT05078866
Study groupRoleWhat they receive
Part I (GAd20-209-FSPs, MVA-209-FSPs)ExperimentalPatients receive GAd20-209-FSPs IM on day 1 and MVA-209-FSPs IM at week 8. Patients undergo endoscopy with biopsy during screening and follow up as well as blood sample collection on the trial.
Receives: Biological: Adenoviral Tumor-specific Neoantigen Priming Vaccine GAd-209-FSP; Procedure: Biospecimen Collection; Procedure: Endoscopic Biopsy; Biological: MVA Tumor-specific Neoantigen Boosting Vaccine MVA-209-FSP; Other: Questionnaire Administration
Part II Arm A (GAd20-209-FSPs, MVA-209-FSPs)ExperimentalPatients receive GAd20-209-FSPs IM at week 52 and MVA-209-FSPs IM at week 60. Patients undergo endoscopy with biopsy as well as blood sample collection on the trial.
Receives: Biological: Adenoviral Tumor-specific Neoantigen Priming Vaccine GAd-209-FSP; Procedure: Biospecimen Collection; Procedure: Endoscopic Biopsy; Biological: MVA Tumor-specific Neoantigen Boosting Vaccine MVA-209-FSP; Other: Questionnaire Administration
Part II Arm B (MVA-209-FSPs)ExperimentalPatients receive MVA-209-FSPs IM at week 52. Patients undergo endoscopy with biopsy as well as blood sample collection on the trial.
Receives: Procedure: Biospecimen Collection; Procedure: Endoscopic Biopsy; Biological: MVA Tumor-specific Neoantigen Boosting Vaccine MVA-209-FSP; Other: Questionnaire Administration

What is being measured

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

  1. Rates of grade 2/3 adverse events and symptom reactivity following vaccination

    Measured: Up to 12 months

  2. Rate of immunogenicity following vaccination (Cohort I)

    Immunogenicity will be defined as reactivity to at least 1 of 16 synthetic FSP pools using an enzyme-linked immune absorbent spot (ELISpot) assay. The rate of immunogenicity induced by Nous-209 will be reported along with its 95% exact (Clopper-Pearson) confidence interval.

    Measured: Baseline and week 9

  3. Rate of immunogenicity following revaccination (Cohort II)

    Immunogenicity will be defined as reactivity to at least 1 of 16 synthetic FSP pools using an enzyme-linked immune absorbent spot (ELISpot) assay. The rate of immunogenicity induced by Nous-209 will be reported along with its 95% exact (Clopper-Pearson) confidence interval.

    Measured: Weeks 52 and at 8 weeks after the last boost with MVA-209-FSP (corresponding to week 68 and week 60, for arm A and B, respectively)

  4. Rates of grade 2/3 adverse events and symptom reactivity following revaccination (Cohort II)

    Measured: Up to 12 months

Secondary outcomes (9)

  1. Changes in T cell immune profile and T cell receptor (TCR) repertoire in the peripheral blood

    Measured: Baseline up to 12 months

  2. Changes in TCR repertoire within histologically normal colorectal mucosal

    Measured: Baseline to 12 months

  3. Changes in the gene expression profile and TCR repertoire of tumor infiltrating lymphocytes (TIL) within colorectal adenomas

    Measured: Baseline to 12 months

  4. T cell cytotoxicity against matched colorectal adenoma organoids

    Measured: At 12 months

  5. Percentage change in the number of colorectal adenomas, advanced neoplasia, and/or carcinomas

    Will use two-sample t-test and general linear models for the comparison.

    Measured: At 12 months

  6. Rate of Lynch syndrome-related carcinomas

    Measured: At 12 months

  7. Change in cell free deoxyribonucleic acid (cfDNA) detectability and mutation profile in the peripheral blood

    Measured: Baseline up to 12 months

  8. Immune response to Nous-209

    Tobacco and alcohol consumption will be correlated with the immune response to Nous-209 in trial participants.

    Measured: Up to 12 months

  9. Mismatch repair and/or microsatellite instability status of polyps (and adjacent normal mucosa as control)

    Will be assessed using different technologies such as immunohistochemistry, MSI analysis by polymerase chain reaction, or next-generation sequencing.

    Measured: Baseline to 12 months

Timeline

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

  1. First posted15 Oct 2021
  2. Study start10 Nov 2022
  3. Primary completion16 Apr 2025
  4. Study completion30 Sep 2026 (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 1/2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05078866
Sponsor's protocol ID
NCI-2021-10799
Other IDs
NCI-2021-10799, 2022-0065, MDA21-06-01, P30CA016672, UG1CA242609
Status last verified
Feb 2026
First submitted
14 Oct 2021
Last updated
3 Mar 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

  • D'Alise AM, Willis J, Duzagac F, Hall MJ, Cruz-Correa M, Idos GE, Thirumurthi S, Ballester V, Leoni G, Garzia I, Antonucci L, De Marco L, Micarelli E, Deng N, Secli L, Gogov S, Dong W, Jack Lee J, Bowen CM, Vornik LA, Garcia-Gonzalez A, Reyes-Uribe L, Richmond E, Umar A, Brown PH, Sinha KM, Rodriguez LM, Scarselli E, Vilar E. Nous-209 neoantigen vaccine for cancer prevention in Lynch syndrome carriers: a phase 1b/2 trial. Nat Med. 2026 Mar;32(3):1002-1011. doi: 10.1038/s41591-025-04182-9. Epub 2026 Jan 16.

    PubMed 41545594

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Adenoviral Tumor-specific Neoantigen Priming Vaccine GAd-209-FSP, Biospecimen Collection and Endoscopic Biopsy in people with Colorectal Carcinoma and Lynch Syndrome, run by National Cancer Institute (NCI) at 4 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 31 inclusion and 12 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 3 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Rates of grade 2/3 adverse events and symptom reactivity following vaccination (time frame: Up to 12 months). The study lists 4 primary outcomes in all. 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 NCT05078866, 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 3 Mar 2026.

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