<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background:</jats:title> <jats:p>This study will evaluate the safety and efficacy of durvalumab in combination with lenvatinib in participants with locally advanced hepatocellular carcinoma before liver transplant and metastatic unresectable HCC. The primary hypothesis of this study is that patients with locally advanced HCC could benefit from durvalumab plus lenvatinib before liver transplant; patients with metastatic unresectable HCC could also benefit from durvalumab plus lenvatinib concerning: 1) Progression-Free Survival (PFS); or recurrence-free survival (RFS) if patients with locally advanced HCC underwent liver transplant; 2) Objective Response Rate (ORR), and 3) Overall survival (OS).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>The investigators design a clinical study to explore whether the combination above as a treatment in patients with advanced and recurrent endometrial carcinoma could prolong PFS and analyze potential immune biomarkers of therapeutic response. This trial is designed as a prospective, open-label study for patients with locally advanced hepatocellular carcinoma before liver transplant and metastatic unresectable HCC (NCT04443322).</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>20 patients with pathologically or cytologically proved locally advanced or metastatic hepatocellular carcinoma were recruited. The combination therapy of Lenvatinib 80–120mg daily orally and durvalumab 1500mg by IV infusion every 4 weeks were performed. PFS and RFS were evaluated as the primary endpoint. ORR, OS, and Percentage of Participants who Experience an Adverse Event (AE) were assessed as the secondary endpoints.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>Durvalumab, combined with Lenvatinib in participants with locally advanced and metastatic hepatocellular carcinoma, is safe and effective.</jats:p> </jats:sec>