Evaluate Durvalumab and Tremelimumab +/- Lenvatinib in Combination With TACE in Patients With Locoregional HCC (EMERALD-3)

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)

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

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Tremelimumab; Drug: Durvalumab; Procedure: Transarterial Chemoembolization (TACE); Drug: Lenvatinib

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 725
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • Recruiting
    • Research Site
  • Gent, Belgium, 9000
    • Recruiting
    • Research Site
• Brazil
  • Barretos, Brazil, 14784-400
    • Active, not recruiting
    • Research Site
  • Brasilia, Brazil, 71681-603
    • Active, not recruiting
    • Research Site
  • Niterói, Brazil, 24020-096
    • Active, not recruiting
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Active, not recruiting
    • Research Site
  • Rio de Janeiro, Brazil, 20231-050
    • Active, not recruiting
    • Research Site
  • Santa Maria, Brazil, 97015-450
    • Active, not recruiting
    • Research Site
  • Santo Andre, Brazil, 09060-650
    • Active, not recruiting
    • Research Site
  • São Paulo, Brazil, 04014-002
    • Suspended
    • Research Site
  • Vitória, Brazil, 29043-272
    • Active, not recruiting
    • Research Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Recruiting
      • Research Site
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Recruiting
      • Research Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Recruiting
      • Research Site
  • Ontario
    • Kingston, Ontario, Canada, K7L 5P9
      • Recruiting
      • Research Site
    • London, Ontario, Canada, N6C 2R5
      • Withdrawn
      • Research Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • Research Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Research Site
    • Montreal, Quebec, Canada, H2X 3E4
      • Recruiting
      • Research Site
• China
  • Beijing, China, 100142
    • Active, not recruiting
    • Research Site
  • Beijing, China, 100021
    • Active, not recruiting
    • Research Site
  • Beijing, China, 100069
    • Active, not recruiting
    • Research Site
  • Changchun, China, 130021
    • Active, not recruiting
    • Research Site
  • Changsha, China, 410013
    • Active, not recruiting
    • Research Site
  • Chengdu, China, 610041
    • Active, not recruiting
    • Research Site
  • Fuzhou, China, 350011
    • Active, not recruiting
    • Research Site
  • Fuzhou, China, 350001
    • Active, not recruiting
    • Research Site
  • Guangzhou, China, 510060
    • Active, not recruiting
    • Research Site
  • Guangzhou, China, 510515
    • Active, not recruiting
    • Research Site
  • Haikou, China, 570311
    • Active, not recruiting
    • Research Site
  • Hangzhou, China, 310022
    • Active, not recruiting
    • Research Site
  • Harbin, China, 150081
    • Active, not recruiting
    • Research Site
  • Hefei, China, 230031
    • Active, not recruiting
    • Research Site
  • Lanzhou, China, 730030
    • Active, not recruiting
    • Research Site
  • Lishui, China, 323000
    • Active, not recruiting
    • Research Site
  • Nanchang, China, 330006
    • Active, not recruiting
    • Research Site
  • Nanjing, China, 210002
    • Active, not recruiting
    • Research Site
  • Nantong, China, 226361
    • Active, not recruiting
    • Research Site
  • Neijiang, China, 641000
    • Active, not recruiting
    • Research Site
  • Shanghai, China, 200032
    • Active, not recruiting
    • Research Site
  • Suzhou, China, 215004
    • Active, not recruiting
    • Research Site
  • Tianjin, China, 300170
    • Active, not recruiting
    • Research Site
  • Urumqi, China, 830000
    • Withdrawn
    • Research Site
  • Wenzhou, China, 325000
    • Active, not recruiting
    • Research Site
  • Wuhan, China, 430010
    • Withdrawn
    • Research Site
  • Wuhan, China, 430010
    • Active, not recruiting
    • Research Site
  • Wuhan, China, 430022
    • Active, not recruiting
    • Research Site
  • Xi'an, China, 710000
    • Active, not recruiting
    • Research Site
  • Zhengzhou, China, 450008
    • Active, not recruiting
    • Research Site
  • Zhengzhou, China, 450000
    • Withdrawn
    • Research Site
  • Zhuhai, China, 519000
    • Active, not recruiting
    • Research Site
• Egypt
  • Alexandria, Egypt, 21131
    • Not yet recruiting
    • Research Site
  • Cairo, Egypt, 11451
    • Not yet recruiting
    • Research Site
  • Luxor, Egypt, 85863
    • Not yet recruiting
    • Research Site
  • Mansoura, Egypt, 7650001
    • Not yet recruiting
    • Research Site
  • New Cairo, Egypt, 11566
    • Not yet recruiting
    • Research Site
  • Shebeen El Kom, Egypt, 32511
    • Not yet recruiting
    • Research Site
• France
  • Angers, France, 49933
    • Recruiting
    • Research Site
  • Clichy, France, 92110
    • Recruiting
    • Research Site
  • Creteil, France, 94010
    • Recruiting
    • Research Site
  • MONTPELLIER Cedex 5, France, 34295
    • Recruiting
    • Research Site
  • Nantes cedex 1, France, 44093
    • Recruiting
    • Research Site
  • Nice, France, 06200
    • Recruiting
    • Research Site
  • Paris, France, 75013
    • Recruiting
    • Research Site
  • Rennes, France, 35000
    • Withdrawn
    • Research Site
  • Strasbourg, France, 67091
    • Recruiting
    • Research Site
  • Toulouse, France, 31059
    • Recruiting
    • Research Site
  • Vandoeuvre Les Nancy, France, 54511
    • Recruiting
    • Research Site
• Germany
  • Bonn, Germany, 53127
    • Recruiting
    • Research Site
  • Chemnitz, Germany, 09116
    • Recruiting
    • Research Site
  • Dresden, Germany, 01307
    • Recruiting
    • Research Site
  • Düsseldorf, Germany, 40225
    • Recruiting
    • Research Site
  • Frankfurt, Germany, 60596
    • Recruiting
    • Research Site
  • Göttingen, Germany, 37075
    • Recruiting
    • Research Site
  • Hamburg, Germany, 22291
    • Recruiting
    • Research Site
  • Hannover, Germany, 30625
    • Recruiting
    • Research Site
  • Heidelberg, Germany, 69120
    • Recruiting
    • Research Site
  • Kiel, Germany, 24105
    • Recruiting
    • Research Site
  • Leipzig, Germany, 04103
    • Recruiting
    • Research Site
  • Magdeburg, Germany, 39120
    • Recruiting
    • Research Site
  • Ulm, Germany, 89081
    • Recruiting
    • Research Site
• India
  • Ahmedabad, India, 380052
    • Recruiting
    • Research Site
  • Ahmedabad, India, 380054
    • Active, not recruiting
    • Research Site
  • Ahmedabad, India, 380060
    • Active, not recruiting
    • Research Site
  • Bangalore, India, 560092
    • Withdrawn
    • Research Site
  • Bangalore, India, 560027
    • Active, not recruiting
    • Research Site
  • Delhi, India, 110029
    • Active, not recruiting
    • Research Site
  • Gurgaon, India, 122002
    • Withdrawn
    • Research Site
  • Gurugram, India, 122001
    • Recruiting
    • Research Site
  • Hyderabad, India, 500032
    • Active, not recruiting
    • Research Site
  • JAipur, India, 302022
    • Active, not recruiting
    • Research Site
  • Kolkata, India, 700099
    • Active, not recruiting
    • Research Site
  • Ludhiana, India, 141001
    • Withdrawn
    • Research Site
  • Mumbai, India, 400012
    • Active, not recruiting
    • Research Site
  • Nagpur, India, 440001
    • Recruiting
    • Research Site
  • New Delhi, India, 110 085
    • Active, not recruiting
    • Research Site
  • New Delhi, India, 110005
    • Active, not recruiting
    • Research Site
  • Rishikesh, India, 249203
    • Recruiting
    • Research Site
• Italy
  • Arezzo, Italy, 52100
    • Recruiting
    • Research Site
  • Firenze, Italy, 50134
    • Recruiting
    • Research Site
  • Milano, Italy, 20133
    • Recruiting
    • Research Site
  • Milano, Italy, 20132
    • Recruiting
    • Research Site
  • Roma, Italy, 00128
    • Recruiting
    • Research Site
  • Rozzano, Italy, 20089
    • Recruiting
    • Research Site
  • Tricase, Italy, 73039
    • Recruiting
    • Research Site
• Japan
  • Chuo-ku, Japan, 104-0045
    • Recruiting
    • Research Site
  • Fukuoka-shi, Japan, 810-8563
    • Recruiting
    • Research Site
  • Hiroshima-shi, Japan, 734-8551
    • Recruiting
    • Research Site
  • Kashihara-shi, Japan, 634-8522
    • Recruiting
    • Research Site
  • Kashiwa, Japan, 277-8577
    • Recruiting
    • Research Site
  • Kumamoto-shi, Japan, 860-8556
    • Recruiting
    • Research Site
  • Mitaka-shi, Japan, 181-8611
    • Recruiting
    • Research Site
  • Morioka-shi, Japan, 028-3695
    • Recruiting
    • Research Site
  • Musashino-shi, Japan, 180-8610
    • Recruiting
    • Research Site
  • Okayama-shi, Japan, 700-8558
    • Recruiting
    • Research Site
  • Osaka-shi, Japan, 543-8555
    • Recruiting
    • Research Site
  • Osaka-shi, Japan, 545-8586
    • Recruiting
    • Research Site
  • Osakasayama-shi, Japan, 589-8511
    • Recruiting
    • Research Site
  • Sapporo-shi, Japan, 006-8555
    • Recruiting
    • Research Site
  • Sendai-shi, Japan, 980-0873
    • Recruiting
    • Research Site
  • Sunto-gun, Japan, 411-8777
    • Recruiting
    • Research Site
  • Tokushima-shi, Japan, 770-8503
    • Recruiting
    • Research Site
  • Tsu-shi, Japan, 514-8507
    • Recruiting
    • Research Site
  • Yokohama-shi, Japan, 241-8515
    • Recruiting
    • Research Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Active, not recruiting
    • Research Site
  • Daegu, Korea, Republic of, 42601
    • Active, not recruiting
    • Research Site
  • Goyang-si, Korea, Republic of, 10408
    • Active, not recruiting
    • Research Site
  • Jung-gu, Korea, Republic of, 41944
    • Active, not recruiting
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Active, not recruiting
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Active, not recruiting
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Active, not recruiting
    • Research Site
• Malaysia
  • George Town, Malaysia, 10450
    • Active, not recruiting
    • Research Site
  • Kuala Lumpur, Malaysia, 59100
    • Active, not recruiting
    • Research Site
  • Kuching, Malaysia, 93586
    • Active, not recruiting
    • Research Site
  • Puncak Alam, Malaysia, 42300
    • Active, not recruiting
    • Research Site
  • Selangor, Malaysia, 62250
    • Active, not recruiting
    • Research Site
• Mexico
  • Guadalajara, Jalisco, Mexico, 44280
    • Active, not recruiting
    • Research Site
  • México, Mexico, 1400
    • Completed
    • Research Site
  • San Luis Potosí, Mexico, 78209
    • Active, not recruiting
    • Research Site
  • Tuxtla Gutierrez, Mexico, 29090
    • Active, not recruiting
    • Research Site
• Philippines
  • Davao City, Philippines, 8000
    • Active, not recruiting
    • Research Site
  • Makati, Philippines, 1229
    • Active, not recruiting
    • Research Site
  • Manila, Philippines, 1003
    • Active, not recruiting
    • Research Site
  • Pasig City, Philippines, 1600
    • Active, not recruiting
    • Research Site
  • Quezon City, Philippines, 1112
    • Active, not recruiting
    • Research Site
• Portugal
  • Lisboa, Portugal, 1649-035
    • Recruiting
    • Research Site
  • Vila Real, Portugal, 5000-508
    • Recruiting
    • Research Site
• Puerto Rico
  • Hato Rey Central, Puerto Rico, 00917
    • Recruiting
    • Research Site
  • San Juan, Puerto Rico, 00927
    • Recruiting
    • Research Site
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Withdrawn
    • Research Site
  • Moscow, Russian Federation, 143442
    • Withdrawn
    • Research Site
• Saudi Arabia
  • Ar Riyāḑ, Saudi Arabia, 11426
    • Recruiting
    • Research Site
  • Dammam, Saudi Arabia, 31444
    • Recruiting
    • Research Site
  • Jeddah, Saudi Arabia, 22384
    • Recruiting
    • Research Site
  • Riyadh, Saudi Arabia, 12713
    • Recruiting
    • Research Site
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Research Site
  • Barcelona, Spain, 8035
    • Recruiting
    • Research Site
  • Cordoba, Spain, 14004
    • Recruiting
    • Research Site
  • Madrid, Spain, 28007
    • Recruiting
    • Research Site
  • Madrid, Spain, 28034
    • Recruiting
    • Research Site
  • San Sebastian, Spain, 20014
    • Recruiting
    • Research Site
• Taiwan
  • Taichung, Taiwan, 40447
    • Recruiting
    • Research Site
  • Taichung, Taiwan, 40705
    • Active, not recruiting
    • Research Site
  • Tainan City, Taiwan, 70403
    • Active, not recruiting
    • Research Site
  • Taipei, Taiwan, 100
    • Active, not recruiting
    • Research Site
  • Taipei, Taiwan, TAIWAN
    • Active, not recruiting
    • Research Site
  • Taoyuan, Taiwan, 333
    • Active, not recruiting
    • Research Site
• Thailand
  • Bangkok, Thailand, 10210
    • Active, not recruiting
    • Research Site
  • Bangkok, Thailand, 10400
    • Active, not recruiting
    • Research Site
  • Bangkok, Thailand, 10700
    • Active, not recruiting
    • Research Site
  • Bangkok, Thailand, 10300
    • Active, not recruiting
    • Research Site
  • Chiang Mai, Thailand, 50200
    • Active, not recruiting
    • Research Site
  • Hat Yai, Thailand, 90110
    • Active, not recruiting
    • Research Site
  • Khon Kaen, Thailand, 40002
    • Active, not recruiting
    • Research Site
  • Phisanulok, Thailand, 65000
    • Withdrawn
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • Research Site
    • Mobile, Alabama, United States, 36607
      • Recruiting
      • Research Site
  • Arizona
    • Yuma, Arizona, United States, 85364
      • Recruiting
      • Research Site
  • California
    • Glendale, California, United States, 91204
      • Recruiting
      • Research Site
  • Florida
    • Weston, Florida, United States, 33331
      • Withdrawn
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Recruiting
      • Research Site
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Recruiting
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • Research Site
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Recruiting
      • Research Site
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Research Site
    • New York, New York, United States, 10029
      • Not yet recruiting
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97213
      • Withdrawn
      • Research Site
    • Portland, Oregon, United States, 97225
      • Withdrawn
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Recruiting
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75235
      • Not yet recruiting
      • Research Site
    • Houston, Texas, United States, 77030
      • Recruiting
      • Research Site
• Vietnam
  • Ha Noi, Vietnam, 100000
    • Active, not recruiting
    • Research Site
  • Hanoi, Vietnam, 100000
    • Active, not recruiting
    • Research Site
  • Hcmc, Vietnam, 700000
    • Active, not recruiting
    • Research Site
  • Hcmc, Vietnam, 70000
    • Active, not recruiting
    • Research Site
  • Ho Chi Minh, Vietnam, 700000
    • Active, not recruiting
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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
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 A vs Arm C	OS is defined as the time from the date of randomization until 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

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): February 26, 2027

Study Registration Dates

• First Submitted: March 21, 2022
• First Submitted That Met QC Criteria: March 21, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Lenvatinib; Liver Cancer; TACE; Durvalumab; Locoregional HCC; Tremelimumab
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Durvalumab; Tremelimumab; Lenvatinib
• Other Study ID Numbers: D910VC00001; 2021-003822-54 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No