There are several clinical trials underway for patients who’ve been diagnosed with Lynch syndrome (LS). These trials are studying prevention methods.

Clinical Trial of Naproxen or Aspirin for Cancer Immune Interception in Lynch Syndrome

NCT05411718

This phase IIa trial at the MD Anderson Cancer Center (Houston, Texas) tests naproxen or aspirin on the normal colon in patients with Lynch syndrome. Since Lynch syndrome is a genetic condition that increases the risk of various types of cancers, especially colorectal and endometrial cancers, the goal of this study is to determine whether taking naproxen or aspirin may help prevent the development of cancerous cells in the colons of people with this risk factor.

Participants in this trial must have Lynch syndrome. They must not have evidence of active/recurrent malignant disease for six months and be at least six months from any prior cancer-directed treatment. They will be randomly assigned to take two naproxen or two aspirin matching capsules by mouth 1 time every day for approximately 1 year. This study has “triple masking,” which means that all three parties involved in the clinical trial (participant, care provider, and investigator) will not know which treatment the participant is receiving.

Naproxen and aspirin are anti-inflammatory drugs that may have anti-cancer effects by modulating the immune system and reducing inflammation.

Aspirin has been shown to reduce the risk of colorectal cancer in people with Lynch syndrome. Updated analyses of a large study called the CAPP2 trial, with all participants having surpassed 10 years of follow-up, show that people with Lynch syndrome who took aspirin daily had a 35% lower risk of developing colorectal cancer than those who did not take aspirin.

Regarding naproxen, a trial (NCT02052908) has shown recently that this common pain reliever is safe to take daily and activates immune pathways in the colorectal mucosa of people living with Lynch syndrome.

Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients

NCT05078866

This 45-participant phase Ib/II trial evaluates the safety and effect of the Nous-209 vaccine in Lynch syndrome patients. Lynch syndrome is an inherited condition, where people affected have a higher chance of developing colorectal cancer and certain other types of cancer at a young age. In Lynch syndrome, because of specific Lynch syndrome mutations, abnormal proteins called “neoantigens” that are different from normal cellular proteins are produced.

Neoantigens are recognized by the body’s immune system as foreign, and the body tries to get rid of them. Tumors arise when the body is not successful in eliminating cells with neoantigens. Nous-209 is a vaccine made with man-made copies of some of those neoantigens to see if “vaccinating” participants with Lynch syndrome can help with development of an immune response and prevent the development of tumors with these neoantigens. This trial aims to see whether the Nous-209 vaccine is safe to give to patients with Lynch syndrome, and how the immune system of Lynch syndrome patients responds to the Nous-209 vaccine. This trial may help researchers determine whether receiving Nous-209 has an effect on the development of polyps or tumors in the colon.

Eligible participants must have a diagnosis of Lynch syndrome and have no evidence of disease for six months prior to screening and must be at least six months from any prior cancer-directed therapy.

Get the complete list of inclusion/exclusion criteria.

The main objectives of this trial are 1) to check the safety and tolerability of the adenoviral tumor-specific neoantigen priming vaccine GAd-209-FSP (1 prime) and MVA tumor-specific neoantigen boosting vaccine MVA-209-FSP (1 boost) when given as a single agent in participants with Lynch syndrome (LS); and 2) to see immune responses to it in the participants.

Participants will receive the prime dose on day 1 and the booster at week 8.

The main trial outcomes are the 1) rates of adverse-events and symptom reactivity, and 2) the rate of immunogenicity after vaccination.

Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome

NCT05419011

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

This 186-participant phase IIb trial tests whether the trivalent Tri-Ad5 vaccine in combination with N-803, an immune enhancer, works to prevent colon and other cancers in people with Lynch syndrome. There are three injections in Tri-Ad5 vaccine, which contains a different component that is in precancer and cancer cells. The idea is that vaccinating with these may cause the immune system to develop an immune response to these, so it can recognize and destroy any precancer and cancer cells that produce these components in the future. The hope is that 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.

The main objective of this trial is to find out if the combination of the trivalent adenovirus-5 (Tri-Ad5) vaccines and the immune enhancer N-803 reduce the incidence of colorectal cancer in patients with Lynch syndrome. This trial will also look at the safety and tolerability of this combination; the effect of other factors like smoking, use of pain reliever drugs and alcohol on the immune response; and the effect of this vaccine on the development of extra-colonic tumors.

To be eligible, participants must have Lynch syndrome and part of the colon and/or rectum intact.

Get a complete list of inclusion and exclusion criteria.

The trial has safety phase I and II parts. In the safety phase I and II, participants will get the trivalent vaccine as a subcutaneous injection 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.

In the randomized control phase, participants are randomized to the experimental or placebo arms. In arm I, they will receive Tri-Ad5 SC and N-803 SC, while in arm II, participants will get the placebo subcutaneously in the same schedule as in the safety phase. They will have similar monitoring with colonoscopies. All participants will have blood sample collection throughout the study.

The main outcome for this trial is the cumulative incidence rate of the composite endpoint of adenomas (tubular, tubulovillous, and serrated), advanced adenomas and colon cancer at 104 weeks.

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