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Ltd."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-na\u00efve patients with uHCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this multicenter, single-arm, phase 2 study, systemic treatment-na\u00efve patients with uHCC received tislelizumab 200\u00a0mg every three weeks plus lenvatinib (bodyweight\u2009\u2265\u200960\u00a0kg: 12\u00a0mg;\u2009&lt;\u200960\u00a0kg: 8\u00a0mg; once daily). Dose-limiting toxicities (DLTs) were evaluated in safety run-in phase to determine whether to enter the expansion phase. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Based on Simon\u2019s two-stage design,\u2009&gt;\u20096 responders were needed in stage 1 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200930) to continue the study, and\u2009\u2265\u200918 responders were needed by the end of stage 2 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200960) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200962). After a median follow-up of 15.7\u00a0months, confirmed ORR and disease control rate were 38.7% (24\/62, 95% confidence interval [CI], 26.6\u201351.9) and 90.3% (56\/62, 95% CI, 80.1\u201396.4), respectively. Median progression-free survival was 8.2\u00a0months (95% CI, 6.8\u2013not evaluable). Overall survival rate at 12\u00a0months was 88.6% (95% CI, 77.7\u201394.4). Grade\u2009\u2265\u20093 treatment-related adverse events occurred in 18 (28.1%) patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov (NCT 04401800).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12916-024-03356-5","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T20:01:23Z","timestamp":1713816083000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Efficacy and safety of tislelizumab plus lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma: a multicenter, single-arm, phase 2 trial"],"prefix":"10.1186","volume":"22","author":[{"given":"Li","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yabing","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minshan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"key":"3356_CR1","unstructured":"Global Cancer Observatory. 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The authors declare that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human research and with the Helsinki Declaration. All procedures involving human subjects\/patients had been approved by the ethics committees of each study site, including the ethics committee of the Sun Yat-sen University Cancer Center (ref: A2020-021\u201301), the Nanfang Hospital of Southern Medical University (ref: NFEC-2020\u2013080), the West China Hospital of Sichuan University (ref: 2020\u201374), the Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (ref: XHEC-A-2020\u2013011-2), the Harbin Medical University Cancer Hospital (ref: 2020\u201356), Peking Union Medical College Hospital (ref: HS2020025), the Second Affiliated Hospital of Zhejiang University School of Medicine (ref: 2020\u2013260), the Anhui Provincial Hospital (ref: 2020\u2013190), and the First Affiliated Hospital of Xi\u2019an Jiaotong University (ref: XJTU1AF2020LSY-52).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All patients had provided informed consent for the participants in the study and publication of any associated data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All the authors declare no conflict of interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"172"}}