Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome

• Status: Not yet recruiting
• Trial end date: 2026-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase IIb trial tests whether Tri-Ad5 in combination with N-803 works to prevent colon and other cancer in patients 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 change of developing colon and other cancer in patients with Lynch syndrome.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Vaccines

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 adenoma(s) and/or >= 1 advanced adenoma(s) and/or colon 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)

• 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)

• Participants older than 18 years will be enrolled. Because the risk of LS related cancers is very low in participants < 18 years of age, children 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 within normal institutional limits

• 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 within normal institutional limits

• 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 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 including, but not limited to, ongoing or active infection, active autoimmune diseases, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, 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 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