{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T06:09:13Z","timestamp":1779170953763,"version":"3.51.4"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Lynch syndrome (LS) is a hereditary cancer syndrome that increases risk for colorectal and other cancers. We hypothesize that vaccines against tumor-associated antigens CEA, MUC1, and brachyury, simultaneously delivered in an adenovirus serotype-5 vector (Tri-Ad5) combined with the immune-enhancing IL-15 receptor superagonist nogapendekin-alfa-inbakicept (NAI) will reduce the incidence of colorectal neoplasms in LS carriers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this ongoing phase IIB double-blind placebo-controlled trial, two open-label safety phases (SPs) assessed safety of Tri-Ad5 alone (SP1, n=10) and with added NAI (SP2, n=10). A randomized controlled trial (RCT) follows the SPs. After baseline colonoscopy, vaccine dosing occurs at weeks 0, 4 and 8; Tri-Ad5 alone in SP1 and Tri-Ad5 plus NAI in SP2, with identical boosters at Week 52. The RCT phase participants (n=138) were randomized to receive Tri-Ad5 plus NAI or placebo. All participants complete colonoscopy at Weeks 52 and 104 for assessment of the primary endpoint: cumulative colorectal neoplasm incidence. Secondary endpoints include safety, tolerability, and immunogenicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All 20 SP participants (median age 57.5 (range 42\u201375), 70% female, 15% minority) received all prime and booster series. SP1 participants reported 139 adverse events (AEs) and SP2 participants reported 178. AEs were predominantly grade 1; no treatment-related serious adverse events (SAEs) occurred. The most common treatment-related AEs were reactogenic events including grade 3 rash (without skin necrosis or breakdown) at NAI injection site (100% of SP2 participants). The RCT phase (n=138) recently completed accrual.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>In LS carriers without active cancer, the combination of Tri-Ad5 + NAI was well-tolerated; the RCT phase is ongoing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/study\/<\/jats:ext-link>\n                      , identifier NCT05419011.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1809281","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:43:06Z","timestamp":1779169386000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Design and preliminary report of a randomized phase IIb clinical trial of multitargeted recombinant adenovirus 5 vaccines against CEA, MUC1, and brachyury (Tri-Ad5) and the IL-15 receptor superagonist nogapendekin alfa inbakicept in Lynch syndrome (TRIAD5-Plus): the first cross-network trial of the Cancer Prevention Clinical Trials Network (CP-CTNet)"],"prefix":"10.3389","volume":"17","author":[{"given":"Ajay","family":"Bansal","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, University of Kansas Medical Center, and University of Kansas Cancer Center","place":["Kansas City, KS, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena M.","family":"Stoffel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan","place":["Ann Arbor, MI, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramona","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Dana-Farber Cancer Institute","place":["Boston, MA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter P.","family":"Stanich","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center","place":["Columbus, OH, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swati G.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medicine-Gastroenterology, University of Colorado","place":["Aurora, CO, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol A.","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic","place":["Cleveland, OH, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Fox Chase Cancer Center","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aparajita","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, University of California, San Francisco","place":["San Francisco, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa A.","family":"Boardman","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic","place":["Rochester, MN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niloy Jewel","family":"Samadder","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic","place":["Phoenix, AZ, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veroushka","family":"Ballestar","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Puerto Rico Comprehensive Cancer Center","place":["San Juan, Puerto Rico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Muller","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Northwestern University","place":["Chicago, IL, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron James","family":"Scott","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Arizona Cancer Center","place":["Tucson, AZ, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly A.","family":"Benante","sequence":"additional","affiliation":[{"name":"Robert H. 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