{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:06:45Z","timestamp":1791396405312,"version":"4.3.3"},"reference-count":7,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>Newer effective therapies are needed for patients with solid tumors with liver metastases and unresectable hepatocellular carcinoma (HCC).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Part 1 (dose exploration) evaluated intrahepatic talimogene laherparepvec (T-VEC) injection in group A (non-HCC liver metastases) and group B (HCC). Cohorts 1-4 received T-VEC monotherapy; cohorts 5 and 6 received T-VEC+pembrolizumab. Part 2 (dose expansion) evaluated intrahepatic or intratumoral T-VEC+pembrolizumab in non-HCC solid tumors. The primary endpoints were dose-limiting toxicities (DLTs) in part 1; objective response rate (ORR) per modified irRC-RECIST and safety in part 2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Part 1 enrolled 28 and 46 patients to receive T-VEC and T-VEC+pembrolizumab, respectively. Three patients reported DLTs (T-VEC, n\u2005=\u20052 grade 3 abdominal pain and aspartate transaminase increase; T-VEC+pembrolizumab, n\u2005=\u20051 grade 3 cholestatic hepatitis). ORR (secondary endpoint) with T-VEC was 0%; ORR (95% CI) with T-VEC+pembrolizumab was 8.3% (1.0, 27.0) for non-HCC and 13.6% (2.9, 34.9) for HCC. Part 2 enrolled 53 patients; ORR (95% CI) was 0% (0.0, 30.8)-20.0% (0.5, 71.6) across 5 tumor types, with 16.7% (95% CI: 3.6, 41.4) for triple-negative breast cancer with the largest sample size (n\u2005=\u200518). Safety findings were consistent with the therapies administered.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Limited efficacy across tumor types evaluated limit further evaluation of intrahepatic T-VEC+pembrolizumab in this patient population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>ClinicalTrials.gov Identifier<\/jats:title>\n                  <jats:p>NCT02509507.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyae203","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T19:30:23Z","timestamp":1743449423000},"source":"Crossref","is-referenced-by-count":12,"title":["Phase Ib\/II trial of talimogene laherparepvec alone and with pembrolizumab in advanced solid tumors with liver metastases and hepatocellular carcinoma"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2277-4157","authenticated-orcid":false,"given":"Joel Randolph","family":"Hecht","sequence":"first","affiliation":[{"name":"UCLA Jonsson Comprehensive Cancer Center , Santa Monica, CA 90404 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjun","family":"Oberoi","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Vall d\u00b4Hebron Institute of Oncology , Barcelona 08035 ,","place":["Spain"]},{"name":"Department of Medicine, Vall d\u2019Hebron University Hospital , Barcelona 08035 ,","place":["Spain"]},{"name":"Department of Medicine, Universitat Aut\u00f2noma de Barcelona , Barcelona 08193 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Garralda Cabanas","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Vall d\u00b4Hebron Institute of Oncology , Barcelona 08035 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Jae Chon","sequence":"additional","affiliation":[{"name":"CHA Bundang Medical Center, CHA University , Bundang-Gu 13496 ,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Digklia","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lausanne University Hospital , Lausanne 1011 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Rottey","sequence":"additional","affiliation":[{"name":"Department of Oncology, Ghent University Hospital , Ghent 9000 ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Martin Jimenez","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Gregorio Mara\u00f1\u00f3n General University Hospital , Madrid 28007 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marya","family":"Chaney","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. , Rahway, NJ 07065 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Hippenmeyer","sequence":"additional","affiliation":[{"name":"Amgen Inc. , Thousand Oaks, CA 91320 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Amgen Inc. , Thousand Oaks, CA 91320 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Liu","sequence":"additional","affiliation":[{"name":"Amgen Inc. , Thousand Oaks, CA 91320 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Hamidi","sequence":"additional","affiliation":[{"name":"Amgen Inc. , Thousand Oaks, CA 91320 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Chesney","sequence":"additional","affiliation":[{"name":"James Graham Brown Cancer Center, University of Louisville , Louisville, KY 40202 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"issue":"1","key":"2025033003405644100_CIT0001","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"2025033003405644100_CIT0002","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/s41591-020-1131-x","article-title":"Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination","volume":"27","author":"Yu","year":"2021","journal-title":"Nat 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locoregional recurrence of breast cancer","volume":"11","author":"Kai","year":"2021","journal-title":"Sci Rep"},{"issue":"2","key":"2025033003405644100_CIT0006","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/s41591-023-02210-0","article-title":"Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial","volume":"29","author":"Soliman","year":"2023","journal-title":"Nat Med"},{"issue":"2","key":"2025033003405644100_CIT0007","doi-asserted-by":"publisher","first-page":"100884","DOI":"10.1016\/j.esmoop.2023.100884","article-title":"Phase Ib study of talimogene laherparepvec in combination with atezolizumab in patients with triple negative breast cancer and colorectal cancer with liver metastases","volume":"8","author":"Hecht","year":"2023","journal-title":"ESMO Open"}],"container-title":["The 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