Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome

NCT05419011 | Active Not Recruiting Phase 2 DMC FDA Drug

• 10 other identifiers: NCI-2021-14234NCI 21-05-01NCI21-05-01INT21-05-01P30CA060553UG1CA242596UG1CA242609UG1CA242632UG1CA242635UG1CA242643
• Study Type: interventional
• Target: 186
• Locations: 2 countries
• Sites: 14

Brief 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. 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.

Conditions

Colorectal Carcinoma; Colorectal Neoplasm; Lynch Syndrome

Outcome Measures

Primary Outcomes (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.

  At 104 weeks

Secondary Outcomes (4)

• Incidence of adverse events

  Up to 104 weeks

• Association of clinical factors with immune responses

  At 104 weeks

• Incidence of extracolonic neoplasms

  At 104 weeks

• Participants' behavior and experience

  At baseline, 12 weeks and 52 weeks

Other Outcomes (7)

• Tumor antigen specific T cell responses (cell-mediated immunity)

  At weeks 0, 4, 8, and 12

• Circulating anti-MUC1 IgG (antibody-mediated immunity)

  At baseline, 52 weeks, and 104 weeks

• Differential expression analyses

  At baseline, 52 weeks, and 104 weeks

Study Arms (4)

Arm I (Tri-Ad5, N-803)

EXPERIMENTAL

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. Participants undergo blood sample collection throughout the study.

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 COMPARATOR

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Colonoscopy; Drug: Placebo Administration; Other: Questionnaire Administration

Safety phase I (Tri-Ad5)

EXPERIMENTAL

Participants 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.

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)

EXPERIMENTAL

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 weeks and 104 weeks. Participants undergo blood sample collection throughout the study.

Biological: Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Colonoscopy; Drug: Nogapendekin Alfa; Other: Questionnaire Administration

Interventions

Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5 BIOLOGICAL

Given SC

Also known as: 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, Tri-Ad5, TriAd5

Arm I (Tri-Ad5, N-803); Safety phase I (Tri-Ad5); Safety phase II (Tri-Ad5 , N-803)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Arm I (Tri-Ad5, N-803); Arm II (placebo); Safety phase I (Tri-Ad5); Safety phase II (Tri-Ad5 , N-803)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (Tri-Ad5, N-803); Arm II (placebo); Safety phase I (Tri-Ad5); Safety phase II (Tri-Ad5 , N-803)

Questionnaire Administration OTHER

Ancillary studies

Arm I (Tri-Ad5, N-803); Arm II (placebo); Safety phase I (Tri-Ad5); Safety phase II (Tri-Ad5 , N-803)

Colonoscopy PROCEDURE

Undergo SOC colonoscopy

Arm I (Tri-Ad5, N-803); Arm II (placebo); Safety phase I (Tri-Ad5); Safety phase II (Tri-Ad5 , N-803)

Nogapendekin Alfa DRUG

Given nogapendekin alfa inbakicept (N-803) SC

Arm I (Tri-Ad5, N-803); Safety phase II (Tri-Ad5 , N-803)

Placebo Administration DRUG

Given SC

Arm II (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• History of organ allograft or other history of immunodeficiency
• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (14)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

Location

University of Arizona Cancer Center - Prevention Research Clinic

Tucson, Arizona, 85719, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Puerto Rico

San Juan, 00936, Puerto Rico

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis

Interventions

Biopsy; Specimen Handling; Colonoscopy

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Endoscopy; Digestive System Surgical Procedures; Minimally Invasive Surgical Procedures

Study Officials

• Ajay Bansal

  University of Kansas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2022
• First Posted: June 15, 2022
• Study Start: May 8, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

PR (1); US (13)