Evaluate Durvalumab and Tremelimumab +/- Lenvatinib in Combination With TACE in Patients With Locoregional HCC

Study Overview
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Brief Summary
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A global study to evaluate transarterial chemoembolization (TACE) in combination with durvalumab, tremelimumab and lenvatinib therapy in patients with locoregional hepatocellular carcinoma

Detailed Description
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This is a Phase III, parallel, randomized, open-label, sponsor-blinded, 3-arm, multicenter, international study assessing the efficacy and safety of durvalumab + tremelimumab + TACE with or without lenvatinib compared with TACE alone in participants with locoregional HCC not amenable to curative therapy (eg, surgical resection, transplantation, or ablation).

Official Title
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A Phase III, Randomized, Open-Label, Sponsor-Blinded, Multicenter Study of Durvalumab in Combination With Tremelimumab ± Lenvatinib Given Concurrently With TACE Compared to TACE Alone in Patients With Locoregional Hepatocellular Carcinoma (EMERALD-3)

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Tremelimumab
* Drug: Durvalumab
* Procedure: Transarterial Chemoembolization (TACE)
* Drug: Lenvatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No evidence of extrahepatic disease Disease not amenable to curative surgery or transplantation or curative ablation but disease amenable to TACE Child Pugh score class A Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment Measurable disease by Modified Response Criteria in Solid Tumors (mRECIST) criteria Adequate organ and marrow function Exclusion Criteria: History of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardia arrhythmia History of hepatic encephalopathy Major portal vein thrombosis visible on baseline imaging Uncontrolled arterial hypertension Co-infection with HBV and HDV

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Tremelimumab, Durvalumab and Lenvatinib in combination with Transarterial Chemoembolization (TACE) | Drug: Tremelimumab<br>* Tremelimumab IV (intravenous)<br>* Other names: MEDI1123;Drug: Durvalumab<br>* Durvalumab IV (intravenous)<br>* Other names: MEDI4736;Procedure: Transarterial Chemoembolization (TACE)<br>* TACE (chemo and embolic agent injection into the hepatic artery)<br>* Other names: DEB-TACE and cTACE;Drug: Lenvatinib<br>* Lenvatinib (oral)<br>* Other names: Lenvima;|
| Experimental: Arm B<br>Tremelimumab and Durvalumab in combination with Transarterial Chemoemobolization (TACE) | Drug: Tremelimumab<br>* Tremelimumab IV (intravenous)<br>* Other names: MEDI1123;Drug: Durvalumab<br>* Durvalumab IV (intravenous)<br>* Other names: MEDI4736;Procedure: Transarterial Chemoembolization (TACE)<br>* TACE (chemo and embolic agent injection into the hepatic artery)<br>* Other names: DEB-TACE and cTACE;|
| Active Comparator: Arm C<br>Transarterial Chemoembolization (TACE) | Procedure: Transarterial Chemoembolization (TACE)<br>* TACE (chemo and embolic agent injection into the hepatic artery)<br>* Other names: DEB-TACE and cTACE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) for Arm A vs Arm C | PFS is defined as time from randomization until progression per RECIST 1.1 as assessed by BICR or death due to any cause | Approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) for Arm A vs Arm C | OS is defined as the time from the date of randomization until death due to any cause | Approximately 5 years | 
| Progression Free Survival (PFS) for Arm B vs Arm C | PFS is defined as time from randomization until progression per RECIST 1.1 as assessed by BICR or death due to any cause | Approximately 5 years | 
| Overall Survival (OS) for Arm B vs Arm C | OS is defined as the time from the date of randomization until death due to any cause | Approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Locoregional HCC, Durvalumab, Tremelimumab, Lenvatinib, TACE, Liver Cancer