Lenvatinib or Regorafenib for Advanced Hepatocellular Carcinoma After Immunotherapy (REVIVE)
brief summary
The goal of this clinical trial is to learn if lenvatinib or regorafenib can help treat people with advanced liver cancer (hepatocellular carcinoma, HCC) that cannot be removed with surgery after first treatment with immunotherapy-based drug combinations. It will also look at the safety of these treatments. The main questions this study aims to answer are: * How long lenvatinib can delay cancer growth in people with good liver function (Child-Pugh)A after dual immunotherapy * How long people with reduced liver function (Child-Pugh B7-B8) live after treatment with lenvatinib or regorafenib after first-line immunotherapy-based combination treatment * What side effects people experience during treatment * How many people have their tumors shrink or disappear The study has two parts: In REVIVE-1, participants with Child-Pugh A liver function will receive lenvatinib. In REVIVE-2, participants with Child-Pugh B7 to B8 liver function will receive either lenvatinib or regorafenib. Participants will: * take lenvatinib or regorafenib by mouth * visit the clinic regularly for physical exams, blood and urine tests, and safety checks * have computed tomography (CT) scans every 8 weeks to check their cancer * be followed during and after treatment to assess outcomes and side effects
detailed description
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Immune checkpoint inhibitor (ICI)-based combination therapies have become standard first-line treatments for patients with unresectable or metastatic HCC. Several clinical trials have demonstrated survival benefits with these regimens, including atezolizumab plus bevacizumab (IMbrave150), durvalumab plus tremelimumab (HIMALAYA), and nivolumab plus ipilimumab (CheckMate 9DW). As a result, immunotherapy-based combinations are widely used as first-line systemic treatment for advanced HCC.
Despite these advances, most patients eventually experience disease progression and require subsequent systemic therapy. However, prospective evidence regarding optimal second-line treatment after progression on ICI-based therapy remains limited. Multikinase inhibitors such as sorafenib, lenvatinib, and regorafenib were originally approved based on studies conducted before the widespread use of immunotherapy. Therefore, their role after failure of modern ICI-based regimens remains unclear.
In addition, most clinical trials in advanced HCC have primarily enrolled patients with preserved liver function (Child-Pugh A). Evidence for patients with Child-Pugh B liver function is limited, and prospective studies evaluating systemic therapies in this population are scarce.
The REVIVE study is a multicenter phase 2 clinical trial designed to evaluate the efficacy and safety of lenvatinib or regorafenib in patients with unresectable or metastatic hepatocellular carcinoma who have progressed after first-line immunotherapy-based combination therapy.
The study consists of two cohorts.
REVIVE-1 is a prospective, multicenter, single-arm phase 2 cohort evaluating lenvatinib in participants with Child-Pugh A liver function whose disease has progressed after first-line dual immune checkpoint inhibitor therapy.
REVIVE-2 is a multicenter, randomized, non-comparative phase 2 cohort evaluating lenvatinib or regorafenib in participants with Child-Pugh B7 to B8 liver function whose disease has progressed after first-line immunotherapy-based combination therapy.
This study aims to generate prospective evidence regarding the efficacy and safety of lenvatinib and regorafenib as second-line treatments after failure of immunotherapy-based therapy in advanced hepatocellular carcinoma, , particularly in settings where evidence remains limited, such as after dual ICI therapy and in patients with Child-Pugh B liver function.
official title
A Multicenter Phase 2 Study of Lenvatinib or Regorafenib in Patients With Unresectable or Metastatic Hepatocellular Carcinoma Who Progressed After First-Line Immunotherapy-Based Combination Therapy (REVIVE)