{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:30:25Z","timestamp":1787067025327,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009109","name":"Pharmaceuticals Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>\n                      Highly effective second\u2010line treatments for hepatocellular carcinoma remain an unmet need. The GOING investigator\u2010initiated Phase I\/IIa trial evaluated regorafenib plus nivolumab (\n                      <jats:italic>add\u2010on<\/jats:italic>\n                      ) in patients who progressed on sorafenib (Cohort\u2010A) or discontinued atezolizumab\u2010bevacizumab (Cohort\u2010B).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients received regorafenib for two 28\u2010day\u2009cycles, adding nivolumab in cycle 3, until unacceptable adverse events, symptomatic progression, withdrawal or death. Primary endpoint was safety. Secondary endpoints included overall survival, time to progression, post\u2010progression survival, objective response rate and incidence of new\u2010extrahepatic\u2010spread.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 85 patients screened, 67 were enrolled (75.5% BCLC\u2010C). All experienced adverse events and 9% led to discontinuation. Severe treatment\u2010related adverse events occurred in 28.4% overall, 32.1% in Cohort\u2010A, and 14.3% in Cohort\u2010B. Median overall survival was 20.0 (95% CI 11\u201337) months, with 40.6% survival at 36\u2009months. In Cohort\u2010A, median overall survival was 25 (95% CI 14\u201339) months with 45% survival at 36\u2009months, while Cohort\u2010B median overall survival was 8 (95% CI 4\u2013NE) months with 28.6% survival at 24\u2009months. Objective response rate was 16.4%; median time to progression and post\u2010progression survival were 5 (95% CI 4\u20139) months and 14 (95% CI 8\u201333) months. Intrahepatic growth was the most common progression pattern, followed by new\u2010extrahepatic\u2010spread.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>add\u2010on<\/jats:italic>\n                      strategy of regorafenib plus nivolumab in second\u2010line had manageable safety and significant clinical activity with a noteworthy median overall survival of 20\u2009months. Among those progressing on sorafenib, 45% were alive at 3\u2009years. These findings support further evaluation with mechanism\u2010guided trials after progression on immunotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      EudraCT number: 2019\u2010003108\u201010;\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.clinicaltrialsregister.eu\">https:\/\/www.clinicaltrialsregister.eu<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.70578","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T09:57:08Z","timestamp":1772963828000},"page":"955-966","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinical Trial: Early Nivolumab Addition to Regorafenib in Patients With Hepatocellular Carcinoma in Second\u2010Line (The GOING Trial)"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3795-3705","authenticated-orcid":false,"given":"Marco","family":"Sanduzzi\u2010Zamparelli","sequence":"first","affiliation":[{"name":"BCLC Group Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Liver Oncology Unit, Liver Unit Hospital Cl\u00ednic  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Matilla","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD)  Madrid Spain"},{"name":"Gastroenterology and Hepatology Department Hospital General Universitario Gregorio Mara\u00f1\u00f3n  Madrid 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