Vaccine Nous-209 for Lynch Syndrome

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Immunosuppressants, NSAIDs, others

Disqualifiers: Active cancer, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine, Nous-209, which could benefit individuals with Lynch syndrome. Lynch syndrome increases the risk of colon cancer and other cancers. The trial aims to determine the vaccine's safety and its effects on the immune system and the formation of polyps or tumors in the colon. Individuals diagnosed with Lynch syndrome, who have no active cancer, and have not undergone cancer treatment in the last six months might be suitable candidates. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

You may need to stop taking aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) unless it's a low-dose aspirin for heart health. You should discuss this with your doctor and get their approval before stopping any medication.

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

Research shows that the Nous-209 vaccine is safe for people with Lynch syndrome. Previous studies found no serious side effects. Patients generally tolerated the vaccine well, experiencing no major discomfort or health problems. This vaccine aims to help the immune system identify and attack certain cancer-causing proteins, potentially preventing cancer in people with Lynch syndrome. Discussing any concerns with a healthcare provider is important, but current data is promising regarding the safety of Nous-209. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Nous-209 because, unlike traditional treatments for Lynch syndrome that focus on managing symptoms or preventing cancer through surgeries and regular screenings, this vaccine uses a novel approach. It targets cancerous cells by teaching the immune system to recognize and attack tumor-specific mutations found in Lynch syndrome. This method, involving the administration of GAd20-209-FSPs and MVA-209-FSPs, represents a significant shift from traditional surveillance strategies to potentially preventing cancer development. By harnessing the body's own defenses to fight off cancer, Nous-209 offers a promising preventive strategy for individuals with Lynch syndrome.

What evidence suggests that the Nous-209 vaccine might be an effective treatment for Lynch syndrome?

Research has shown that the Nous-209 vaccine may help treat Lynch syndrome by targeting unusual proteins found in these patients. In earlier studies, about 86% of patients who received the vaccine with pembrolizumab had stable disease, meaning their cancer did not worsen. Additionally, 14% of these patients experienced some tumor shrinkage. This suggests the vaccine might help control cancer growth by boosting the immune system to recognize and fight cancer cells. While these results are promising, the vaccine is still being tested in this trial to confirm its effectiveness and safety. Participants in this trial will receive different formulations of the Nous-209 vaccine, such as GAd20-209-FSPs and MVA-209-FSPs, in separate treatment arms to evaluate their effects. ^{1 5 6 7 8}

Who Is on the Research Team?

Eduardo Vilar-Sanchez

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for Lynch syndrome patients without active cancer for 6 months, who can undergo colonoscopy with biopsies yearly. They must be past any cancer treatment by at least 6 months, avoid certain meds, use contraception, and adhere to the study protocol including vaccine cycles and blood sample collection.

Inclusion Criteria

I have been diagnosed with Lynch syndrome based on genetic tests and clinical criteria.

I agree not to take certain medications during the trial.

Participants must have undergone collection of research blood samples at baseline and week 9 for evaluation of the immunogenicity endpoint as specified for Cohort 1

Exclusion Criteria

My biopsy shows high-grade dysplasia or cancer.

Known hypersensitivity reaction to study drug or related substances

I have not received a viral vaccine in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment Part I

Participants receive GAd20-209-FSPs intramuscularly on day 1 and MVA-209-FSPs at week 8. Endoscopy with biopsy and blood sample collection are conducted.

8 weeks

2 visits (in-person)

Treatment Part II

Eligible patients from Part I are randomized to receive either GAd20-209-FSPs and MVA-209-FSPs or MVA-209-FSPs alone at week 52 and week 60. Endoscopy with biopsy and blood sample collection are conducted.

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion at weeks 16, 24, 36, and 52.

52 weeks

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Nous-209

Trial Overview The Nous-209 vaccine's safety and immune response are being tested in this phase Ib/II trial. It involves biospecimen collection, endoscopic biopsy, two types of vaccines (GAd-209-FSP and MVA-209-FSP), and questionnaire administration to see if it affects polyp or tumor development in the colon.

How Is the Trial Designed?

Group I: Part II Arm B (MVA-209-FSPs) Experimental Treatment 4 Interventions

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

Group II: Part II Arm A (GAd20-209-FSPs, MVA-209-FSPs) Experimental Treatment 5 Interventions

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.

Group III: Part I (GAd20-209-FSPs, MVA-209-FSPs) Experimental Treatment 5 Interventions

Patients 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.

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

Lynch Syndrome (LS) is linked to mutations in DNA mismatch repair genes, leading to tumors with high microsatellite instability and increased tumor-specific neoantigens that can be targeted by the immune system.

Current research focuses on identifying these neoantigens for developing preventive vaccines against LS, utilizing both computational prediction methods and experimental validation techniques, with ongoing clinical trials exploring their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in vaccine development for cancer prevention and treatment in Lynch Syndrome. Bolivar, AM., Duzagac, F., Sinha, KM., et al.[2023]

In a study of 56 patients referred for genetic counseling at a Canadian hereditary cancer clinic, Lynch syndrome mutations were confirmed or highly suspected in 14.3% of cases, indicating a significant prevalence in this population.

The most effective referral criteria for identifying individuals at risk for Lynch syndrome were having two or more primary cancers related to Lynch syndrome or two first-degree relatives with such cancers, with positive predictive values of 66.7% and 58.3%, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The identification of Lynch syndrome in British Columbia. Cremin, CM., Armstrong, L., Gill, S., et al.[2021]

In a multicenter study of 1942 Lynch syndrome mutation carriers, significant cancer risks were identified, with colorectal cancer being the most common, showing cumulative incidences at 70 years of 46% for MLH1, 35% for MSH2, 20% for MSH6, and 10% for PMS2 mutation carriers.

Despite frequent colorectal cancer occurrences, the ten-year survival rates were high, at 87% overall, and even higher at 91% for those whose first cancer was colorectal, indicating that while cancer risk is significant, outcomes are generally favorable with proper surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Møller, P., Seppälä, T., Bernstein, I., et al.[2022]

Lynch syndrome (LS), a hereditary cancer syndrome caused by mutations in DNA mismatch repair genes, poses a significant cancer risk, with up to 50% lifetime risk for colorectal and endometrial cancers, highlighting the need for effective prevention strategies.

Recent advances in precision oncology have led to the development of cancer vaccines targeting frameshift peptides (FSP) that are recognized by the immune system, showing promise in clinical trials for LS carriers, with evidence of safety and immunogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lynch syndrome cancer vaccines: A roadmap for the development of precision immunoprevention strategies. Sei, S., Ahadova, A., Keskin, DB., et al.[2023]

Cancer vaccines targeting neoantigens, particularly in mismatch repair-deficient cancers like those associated with Lynch syndrome, show promise due to their ability to elicit strong immune responses from CD8+ cytotoxic T cells.

The predictable nature of mutations in Lynch syndrome allows for the development of a preventive cancer vaccine, with RNA vaccines being highlighted as a particularly effective strategy for immunoprevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccines for immunoprevention of DNA mismatch repair deficient cancers. Hernandez-Sanchez, A., Grossman, M., Yeung, K., et al.[2022]

In a study using a mouse model of Lynch Syndrome, researchers identified a novel tumor neo-antigen from a mutation in the SENP6 gene that could prevent tumor growth, demonstrating the potential for a vaccine to induce a protective immune response against colorectal cancer.

The vaccine elicited a specific CD8+ T cell response, indicating that targeting neoepitopes may offer a promising therapeutic strategy for patients with Lynch Syndrome by enhancing their immune defense against tumor development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

On the development of a neoantigen vaccine for the prevention of Lynch Syndrome. Solomon, A., Alteber, Z., Bassan, D., et al.[2022]

In a study of 8500 carriers of pathogenic MMR variants, it was found that non-colorectal cancers, particularly gynecological cancers, were more frequent and associated with higher mortality than colorectal cancers among those undergoing colonoscopy surveillance.

The research highlights a significant challenge in managing Lynch syndrome, as deaths from non-colorectal cancers outnumber those from colorectal cancers, indicating a need for improved strategies to address these high-mortality cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database. Dominguez-Valentin, M., Haupt, S., Seppälä, TT., et al.[2023]

The study developed an 'off-the-shelf' neoantigen-based vaccine called Nous-209, targeting shared frameshift peptides (FSPs) from 320 microsatellite instability (MSI) tumor biopsies, which could potentially treat and prevent MSI tumors.

Immunogenicity tests in mice showed that Nous-209 effectively induced strong CD8 and CD4 T-cell responses, indicating its potential to elicit a robust immune response against MSI tumors in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Genetic Vaccine Encoding Shared Cancer Neoantigens to Treat Tumors with Microsatellite Instability. Leoni, G., D'Alise, AM., Cotugno, G., et al.[2021]

The study reviewed the records of 464 carriers of Lynch syndrome-related pathogenic variants and found that documentation of risk management strategies improved significantly after the release of guidelines, particularly for colonoscopy and hysterectomy.

Despite high compliance rates for certain strategies like colonoscopy (87%) and hysterectomy (68%), there is still a need for better communication and adherence to all recommended risk management strategies among carriers, suggesting that tailored interventions are necessary to optimize clinician recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of implementation of risk management guidelines for carriers of pathogenic variants in mismatch repair genes: a nationwide audit of familial cancer clinics. Meiser, B., Kaur, R., Kirk, J., et al.[2021]

In a study of 1046 patients with Lynch syndrome, those who also had inflammatory bowel disease (IBD) developed colorectal cancer (CRC) at a younger age (median age 36) compared to those without IBD (median age 46).

Despite the earlier onset of CRC in patients with Lynch syndrome and IBD, the overall cumulative incidence of CRC was similar between both groups, indicating that while age of onset differs, the long-term risk remains comparable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease. Derikx, LA., Smits, LJ., van Vliet, S., et al.[2018]

Defective DNA mismatch repair (dMMR) is linked to various cancers, particularly in individuals with Lynch syndrome, which significantly increases the risk of developing microsatellite unstable cancers (MSI-H) due to recurrent mutations.

While advanced MSI-H tumors can be treated with checkpoint inhibitors, the response rates are only 30-60%. However, there is potential for developing off-the-shelf cancer vaccines targeting specific frameshift mutations that produce shared immunogenic neoantigens, which could improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lynch Syndrome and MSI-H Cancers: From Mechanisms to "Off-The-Shelf" Cancer Vaccines. Roudko, V., Cimen Bozkus, C., Greenbaum, B., et al.[2022]

Lynch syndrome (LS) is an inherited condition that significantly increases the risk of colorectal and endometrial cancers due to mutations in mismatch repair genes, yet it remains underdiagnosed despite guidelines for testing in new cancer cases.

There are promising advancements in the management of LS, including the potential for preventative medications and the development of immunotherapy and anti-cancer vaccines, which could improve treatment outcomes for patients with LS-associated tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lynch syndrome: from detection to treatment. Williams, MH., Hadjinicolaou, AV., Norton, BC., et al.[2023]

Citations

1. firstwordpharma.com firstwordpharma.com/story/6512052

Nouscom to Present New Positive Phase 1b/2 Clinical and ... It affects approximately 1 in 300 people, leading to a significantly increased lifetime cancer risk of up to 80%. While current LS disease ...

2. nouscom.com nouscom.com/2025/10/13/nouscom-presents-positive-phase-2-results-of-nous-209-immunotherapy-combined-with-pembrolizumab-in-msi-h-metastatic-colorectal-cancer-patients-refractory-to-anti-pd-1-therapy-at-esmo-2025/

Nouscom Presents Positive Phase 2 Results of NOUS-209 ... Seven patients (32%) were retreated with NOUS-209 at 6 months; among those, 86% remained in stable disease and 14% had a partial response, with ...

3. finance.yahoo.com finance.yahoo.com/news/nouscom-present-positive-phase-1b-130000577.html

Nouscom to Present New Positive Phase 1b/2 Clinical and ... Nouscom to Present New Positive Phase 1b/2 Clinical and Translational Data on NOUS-209 Immunogenicity and Cancer Interception Potential in Lynch ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05078866

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome ... 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 ...

5. withpower.com withpower.com/trial/phase-2-syndrome-2-2022-525bf

Vaccine Nous-209 for Lynch Syndrome · Info for Participants This trial tests the safety and effectiveness of the Nous-209 vaccine in patients with Lynch syndrome, a condition that increases cancer risk.

6. prevention.cancer.gov prevention.cancer.gov/clinical-trials/clinical-trials-search/nct05078866

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome ... 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 ...

7. nouscom.com nouscom.com/2025/04/29/nouscom-presents-positive-final-results-from-completed-phase-ib-ii-study-of-neoantigen-immunotherapy-nous-209-at-aacr-2025-demonstrating-a-highly-potent-and-durable-immune-response-in-lynch-syndrome-2/

Nouscom Lynch Syndrome (LS) is a common hereditary condition that ... Favorable Safety Profile: NOUS-209 was well tolerated, with no serious ...

8. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A732

638 Nous-209 vaccine induces shared neoantigen ... Nous-209 is a genetic vaccine encoding 209 neoantigens shared across sporadic and hereditary MSI tumors developed for interception and treatment of MSI tumors.