{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:28:12Z","timestamp":1790713692652,"version":"4.1.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":25,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["2017-0014"],"award-info":[{"award-number":["2017-0014"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Checkpoint agonists utomilumab (4-1BB agonist) and ivuxolimab (OX40 agonist) enhance Teffector cell function. Preclinical studies suggest that combining these drugs with avelumab (anti-PD-L1 antibody) can potentially synergize this effect.\u00a0In addition, tissue abscopal effects of radiation therapy may improve antigen presentation, complementing PD-L1 blockade.\u00a0We conducted a single institution, open-label, multi-arm, non-randomized, phase 1\/2 clinical trial of avelumab in combination with ivuxolimab, with or without utomilumab, and radiation therapy in patients with advanced solid tumors. Herein, we present a subgroup analysis in patients with gastrointestinal (GI) tumors (pancreatic, colon, gastric, and hepatocellular).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The primary objectives of this study were to assess safety, tolerability, and dose-limiting toxicities. The secondary objectives were to evaluate efficacy including response rate, progression free survival (PFS), as determined by immune-related Response Criteria in Solid Tumors (irRECIST) and overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty-one patients with pancreatic (n\u2005=\u200521), colorectal (n\u2005=\u20058), hepatocellular (n\u2005=\u20051), and gastric (n\u2005=\u20051) cancers were included in this study. The most common treatment-related adverse events (TRAEs) were chills (13%), diarrhea (10%), colitis (10%), fatigue (6%), and fever (6%). There were 3 instances of grade 3 diarrhea and colitis (10%) without any other grade\u2005\u2265\u20053 TRAEs Among the 24 patients evaluable for response, 9 (37.5%) had immune-related stable disease (irSD) and 14 (58.3%) had immune-related progressive disease (irPD). One patient had clinical progression without radiological confirmation. The median PFS was 2 months. Median OS was 5.6 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Combining avelumab with co-stimulatory checkpoint agonists produces modest activity without added safety concerns in patients with advanced GI malignancies (ClinicalTrials.gov Identifier: NCT03217747).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf032","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T23:20:57Z","timestamp":1738711257000},"source":"Crossref","is-referenced-by-count":3,"title":["A phase I\/II trial of avelumab combinations with ivuxolimab, utomilumab, and radiation therapy in patients with advanced gastrointestinal malignancies"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3412-7689","authenticated-orcid":false,"given":"Jibran","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Knisely","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX 77230 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Torrado","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 ,","place":["United 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J","family":"Koay","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van Karlyle","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9158-0941","authenticated-orcid":false,"given":"Milind","family":"Javle","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A","family":"Wolff","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6816-6072","authenticated-orcid":false,"given":"Funda","family":"Meric-Bernstam","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubham","family":"Pant","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 ,","place":["United 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