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This study aimed to investigate the efficacy and safety of TACE combined with envafolimab and lenvatinib for uHCC. Eligible patients with uHCC received envafolimab and lenvatinib after TACE until disease progression, conversion to surgery, intolerable toxicities, or death. The primary endpoint was the objective response rate (ORR) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Between March 2022 and July 2022, 38 patients were included for safety analysis, and 36 patients were included for efficacy analysis. As of the data cutoff (13 December 2023), the median follow-up was 16.9 months. The ORR was 50%, and disease control rate (DCR) was 83.3% per RECIST 1.1 (ORR and DCR of both 83.3% per modified RECIST (mRECIST)). The median progression-free survival (PFS) was 7.58 months. Of 36 patients, 17 patients were converted to resectable HCC with a surgical conversion rate of 47.2%, and 16 patients underwent surgery with R0 resection rate of 100%, pathologic complete response (pCR) rate of 31.3%. Overall incidences of treatment-related adverse events (TRAEs) of any grade was 97.4%. Grade\u2009\u2265\u20093 TRAEs were observed in 52.6% patients. No treatment-related deaths occurred. Image mass cytometry\n                    <jats:bold>(<\/jats:bold>\n                    IMC) analysis revealed that combined treatment improved the immune status of the tumor microenvironment, and resident macrophages had the potential to predict efficacy of this treatment. Envafolimab plus lenvatinib and TACE yielded promising survival outcomes and conversion efficiency with a tolerable safety profile. Trial registration Clinical trials: NCT05213221.\n                  <\/jats:p>","DOI":"10.1038\/s41392-024-01991-1","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T10:02:31Z","timestamp":1728468151000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Envafolimab plus lenvatinib and transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: a prospective, single-arm, phase II study"],"prefix":"10.1038","volume":"9","author":[{"given":"Yiwen","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendi","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5942-7282","authenticated-orcid":false,"given":"Xiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6325-0766","authenticated-orcid":false,"given":"Jian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunliang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risheng","family":"Que","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuchun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiliang","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aibin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2934-0880","authenticated-orcid":false,"given":"Xueli","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0143-3353","authenticated-orcid":false,"given":"Tingbo","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"1991_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray, F. et al. 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