Assess Efficacy and Safety of Durvalumab Alone or Combined With Bevacizumab in High Risk of Recurrence HCC Patients After Curative Treatment (EMERALD-2)

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multi Center Study of Durvalumab Monotherapy or in Combination With Bevacizumab as Adjuvant Therapy in Patients With Hepatocellular Carcinoma Who Are at High Risk of Recurrence After Curative Hepatic Resection or Ablation

A global study to assess the efficacy and safety of durvalumab in combination with bevacizumab or durvalumab alone in patients with hepatocellular carcinoma who are at high risk of recurrence.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Durvalumab; Drug: Bevacizumab; Other: Placebo

Detailed Description

This is a Phase III, randomized, double-blind, placebo-controlled, multi-center, global study to assess the efficacy and safety of durvalumab in combination with bevacizumab or durvalumab monotherapy or placebo as adjuvant therapy. This study will be conducted in patients with HCC who are at high risk of recurrence after curative hepatic resection or ablation.

• Study Type: Interventional
• Enrollment (Actual): 908
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Kogarah, Australia, 2217
    • Research Site
  • Melbourne, Australia, 3004
    • Research Site
  • Nedlands, Australia, 6009
    • Research Site
  • Westmead, Australia, 2145
    • Research Site
• Austria
  • Innsbruck, Austria, 6020
    • Research Site
  • Linz, Austria, 4010
    • Research Site
  • Sankt Pölten, Austria, 3100
    • Research Site
• Brazil
  • Florianópolis, Brazil, 88034-000
    • Research Site
  • Porto Alegre, Brazil, 90035-003
    • Research Site
  • Porto Alegre, Brazil, 90020-090
    • Research Site
  • Rio de Janeiro, Brazil, 20231-050
    • Research Site
  • Santa Maria, Brazil, 97015-450
    • Research Site
  • Santo André, Brazil, 09060-870
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
  • Vitória, Brazil, 29043-272
    • Research Site
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Research Site
    • Kingston, Ontario, Canada, K7L 2V7
      • Research Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Research Site
  • Quebec
    • Québec, Quebec, Canada, G1R 2J6
      • Research Site
• China
  • Beijing, China, 100142
    • Research Site
  • Beijing, China, 100021
    • Research Site
  • Beijing, China, 100730
    • Research Site
  • Bengbu, China, 233004
    • Research Site
  • Changchun, China, 130021
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  • Changsha, China, 410013
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  • Chengdu, China, 610041
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  • Fuzhou, China, 350005
    • Research Site
  • Guangzhou, China, 510000
    • Research Site
  • Guangzhou, China, 510080
    • Research Site
  • Guangzhou, China, 510515
    • Research Site
  • Hangzhou, China, 310022
    • Research Site
  • Hangzhou, China, 310003
    • Research Site
  • Hangzhou, China, 310016
    • Research Site
  • Harbin, China, 150049
    • Research Site
  • Hefei, China, 230001
    • Research Site
  • Hohhot, China, 010010
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  • Nanjing, China, 210002
    • Research Site
  • Nanjing, China, 2100008
    • Research Site
  • Ningbo, China, 315100
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Shanghai, China, 201114
    • Research Site
  • Shanghai, China, 201318
    • Research Site
  • Tianjin, China, 300170
    • Research Site
  • Wuhan, China, 430079
    • Research Site
  • Xi'an, China, 710061
    • Research Site
  • Zhengzhou, China, 450052
    • Research Site
  • Ürümqi, China, 830000
    • Research Site
• Egypt
  • Alexandria, Egypt, 21131
    • Research Site
  • Asyut, Egypt, 71511
    • Research Site
  • Cairo, Egypt, 11451
    • Research Site
  • Cairo, Egypt, 11588
    • Research Site
  • Cairo, Egypt, 11796
    • Research Site
  • Dakahlia, Egypt, 35516
    • Research Site
  • New Cairo, Egypt, 11566
    • Research Site
  • Shebeen El Kom, Egypt, 32511
    • Research Site
• France
  • Amiens, France, 88054
    • Research Site
  • Angers, France, 49933
    • Research Site
  • Besançon, France, 25000
    • Research Site
  • Clichy, France, 92110
    • Research Site
  • Dijon, France, 21079
    • Research Site
  • Nantes, France, 44093
    • Research Site
  • Nice, France, 06200
    • Research Site
  • Paris, France, 75571
    • Research Site
  • Pessac, France, 33604
    • Research Site
  • Toulouse, France, 31059
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  • Tours, France, 37049
    • Research Site
• Germany
  • Berlin, Germany, 13353
    • Research Site
  • Bonn, Germany, 53105
    • Research Site
  • Chemnitz, Germany, 09116
    • Research Site
  • Cologne, Germany, 50937
    • Research Site
  • Freiburg im Breisgau, Germany, 79106
    • Research Site
  • Heidelberg, Germany, 69120
    • Research Site
  • Leipzig, Germany, 04103
    • Research Site
  • Lübeck, Germany, 23538
    • Research Site
  • München, Germany, 81377
    • Research Site
  • Tübingen, Germany, 72076
    • Research Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site
  • Hong Kong, Hong Kong, 150001
    • Research Site
  • Hong Kong, Hong Kong, 0000
    • Research Site
  • Hong Kong, Hong Kong, 999077
    • Research Site
  • Kwai Chung, Hong Kong, 999077
    • Research Site
  • Shatin, Hong Kong, 00000
    • Research Site
• India
  • Bangalore, India, 560027
    • Research Site
  • Bangalore, India, 560092
    • Research Site
  • Hyderabad, India, 500032
    • Research Site
  • Kolkata, India, 700160
    • Research Site
  • Mumbai, India, 400012
    • Research Site
  • New Delhi, India, 110017
    • Research Site
  • New Delhi, India, 110085
    • Research Site
  • New Delhi, India, 110076
    • Research Site
• Italy
  • Bologna, Italy, 40138
    • Research Site
  • Milan, Italy, 20162
    • Research Site
  • Milan, Italy, 20132
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Roma, Italy, 00168
    • Research Site
  • Tricase, Lecce, Italy, 73039
    • Research Site
  • Verona, Italy, 37134
    • Research Site
• Japan
  • Bunkyō City, Japan, 113-8655
    • Research Site
  • Fukuoka, Japan, 810-8563
    • Research Site
  • Gifu, Japan, 500-8513
    • Research Site
  • Hiroshima, Japan, 734-8551
    • Research Site
  • Kumamoto, Japan, 860-8556
    • Research Site
  • Kurume-shi, Japan, 830-0011
    • Research Site
  • Kyoto, Japan, 606-8507
    • Research Site
  • Kyoto, Japan, 612-8555
    • Research Site
  • Kōtoku, Japan, 135-8550
    • Research Site
  • Matsuyama, Japan, 790-8524
    • Research Site
  • Mitaka-shi, Japan, 181-8611
    • Research Site
  • Musashino-shi, Japan, 180-8610
    • Research Site
  • Nagasaki, Japan, 852-8501
    • Research Site
  • Nagoya, Japan, 466-8560
    • Research Site
  • Nagoya, Japan, 467-8602
    • Research Site
  • Osaka, Japan, 541-8567
    • Research Site
  • Osaka, Japan, 534-0021
    • Research Site
  • Osaka, Japan, 543-8555
    • Research Site
  • Osakasayama-shi, Japan, 589-8511
    • Research Site
  • Sapporo, Japan, 006-8555
    • Research Site
  • Sapporo, Japan, 060-0033
    • Research Site
  • Sendai, Japan, 980-0872
    • Research Site
  • Shinagawa-ku, Japan, 142-8666
    • Research Site
  • Shinjuku-ku, Japan, 162-8655
    • Research Site
  • Shinjuku-ku, Japan, 160-0023
    • Research Site
  • Shiwa-gun, Japan, 028-3695
    • Research Site
  • Takasaki-shi, Japan, 370-0829
    • Research Site
  • Tsu, Japan, 514-8507
    • Research Site
  • Wakayama, Japan, 641-8510
    • Research Site
  • Yokohama, Japan, 241-8515
    • Research Site
  • Yokohama, Japan, 245-8575
    • Research Site
• Peru
  • Lima, Peru, LIMA 34
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  • Lima, Peru, LIMA 41
    • Research Site
  • Lima, Peru, LIMA 31
    • Research Site
  • San Isidro, Peru, 27
    • Research Site
• Philippines
  • City of Muntinlupa, Philippines, 1780
    • Research Site
  • Manila, Philippines, 1000
    • Research Site
  • Pasig, Philippines, 1605
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-796
    • Research Site
  • Gdansk, Poland, 80-952
    • Research Site
  • Poznan, Poland, 61-866
    • Research Site
  • Warsaw, Poland, 02-034
    • Research Site
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Research Site
• Russia
  • Barnaul, Russia, 656049
    • Research Site
  • Moscow, Russia, 125284
    • Research Site
  • Moscow, Russia, 119421
    • Research Site
  • Obninsk, Russia, 249031
    • Research Site
  • Saint Petersburg, Russia, 197758
    • Research Site
  • Saint Petersburg, Russia, 197022
    • Research Site
  • Saint Petersburg, Russia, 197044
    • Research Site
  • Yekaterinburg, Russia, 620905
    • Research Site
• Singapore
  • Singapore, Singapore, 308433
    • Research Site
  • Singapore, Singapore, 119074
    • Research Site
  • Singapore, Singapore, 329563
    • Research Site
• South Korea
  • Busan, South Korea, 49241
    • Research Site
  • Daegu, South Korea, 41944
    • Research Site
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 05505
    • Research Site
  • Seoul, South Korea, 06351
    • Research Site
• Taiwan
  • Changhua, Taiwan, 500
    • Research Site
  • Tainan, Taiwan, 710
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Taipei, Taiwan, 11217
    • Research Site
  • Taoyuan, Taiwan, 333
    • Research Site
  • Yunlin, Taiwan, 640
    • Research Site
• Thailand
  • Bangkok, Thailand, 10210
    • Research Site
  • Bangkok, Thailand, 10300
    • Research Site
  • Bangkok, Thailand, 10330
    • Research Site
  • Bangkok, Thailand, 10700
    • Research Site
  • Chiang Mai, Thailand, 50200
    • Research Site
  • Hat Yai, Thailand, 90110
    • Research Site
  • Khon Kaen, Thailand, 40002
    • Research Site
  • Pathum Thani, Thailand, 12120
    • Research Site
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06100
    • Research Site
  • Ankara, Turkey (Türkiye), 6200
    • Research Site
  • Istanbul, Turkey (Türkiye), 34098
    • Research Site
  • Izmir, Turkey (Türkiye), 35100
    • Research Site
  • Malatya, Turkey (Türkiye), 44100
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Research Site
    • Mobile, Alabama, United States, 36604
      • Research Site
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Research Site
  • California
    • Costa Mesa, California, United States, 92627
      • Research Site
    • La Jolla, California, United States, 92093-0698
      • Research Site
    • Long Beach, California, United States, 90806
      • Research Site
    • Orange, California, United States, 92868
      • Research Site
    • Sacramento, California, United States, 95817
      • Research Site
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Research Site
  • Florida
    • Miami, Florida, United States, 33176
      • Research Site
    • Tampa, Florida, United States, 33606
      • Research Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96819
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • Research Site
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Research Site
    • Grand Rapids, Michigan, United States, 49503
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Research Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Research Site
  • New York
    • New York, New York, United States, 10021
      • Research Site
    • Stony Brook, New York, United States, 11794
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Research Site
    • Winston-Salem, North Carolina, United States, 27157
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15212
      • Research Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Research Site
    • Memphis, Tennessee, United States, 38104
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75216
      • Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site
  • Hanoi, Vietnam, 123
    • Research Site
  • Ho Chi Minh City, Vietnam
    • Research Site
  • Ho Chi Minh City, Vietnam, 700000
    • Research Site
  • Hochiminh, Vietnam, 70000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 150 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically (or radiologically for patients undergoing curative ablation), newly diagnosed, confirmed HCC and successfully completed curative therapy (resection or ablation)
• Imaging to confirm disease-free status within 28 days prior to randomization
• ECOG 0-1 at enrolment
• Child-Pugh score of 5 or 6
• Adequate organ and marrow function.

Exclusion Criteria:

• Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC
• Evidence of metastasis, macrovascular invasion or co-existing malignant disease on baseline imaging
• History of hepatic encephalopathy within 12 months prior to randomization
• Evidence, by Investigator assessment, of varices at risk of bleeding on upper endoscopy or contrast-enhanced cross-sectional imaging
• Patients with Vp1 to Vp4 portal vein thrombosis on baseline imaging are excluded
• Active co-infection with HBV and HDV.
• Receipt of prior systemic anticancer therapy for HCC
• Those on a waiting list for liver transplantation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Durvalumab 1120 mg (Q3W) + bevacizumab 15 mg/kg (Q3W)	Drug: Durvalumab; Durvalumab IV (intravenous); Other Names: IMFINZI; Drug: Bevacizumab; Bevacizumab IV (intravenous); Other Names: AVASTIN
Experimental: Arm B; Durvalumab 1120 mg (Q3W) + bevacizumab placebo (Q3W)	Drug: Durvalumab; Durvalumab IV (intravenous); Other Names: IMFINZI; Other: Placebo; Saline solution for Durvalumab and/or Bevacizumab masking (IV intravenous) or Dextrose for Durvalumab masking
Placebo Comparator: Arm C; Durvalumab placebo (Q3W) + bevacizumab placebo (Q3W)	Other: Placebo; Saline solution for Durvalumab and/or Bevacizumab masking (IV intravenous) or Dextrose for Durvalumab masking

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival (RFS) for Arm A vs Arm C	RFS (per RECIST 1.1 criteria as assessed by BICR) will be defined as the time from the date of randomization until the date of the first objective radiologic recurrence or death due to any cause, whichever occurs first.	Up to 49 months after first patient randomized

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival (RFS) Arm B vs Arm C	RFS (per RECIST 1.1 criteria as assessed by BICR) will be defined as the time from the date of randomization until the date of the first objective radiologic recurrence or death due to any cause, whichever occurs first.	Up to 49 months after first patient randomized
Overall Survival (OS) for Arm A vs Arm C and Arm B vs Arm C	OS is defined as the time from the date of randomization until death due to any cause	No timeframe
Recurrence-free survival at 24 months (RFS24) and 36 months (RFS36) for Arm A vs Arm C and Arm B vs Arm C	Proportion of RFS at 24 months and at 36 months	At 24 and at 36 months
Time to recurrence (TTR) for Arm A vs Arm C and Arm B vs Arm C	TTR is defined as the time from the date of randomization until the date of disease recurrence	Up to 49 months after first patient randomized
Time from randomization to recurrence/progression on next therapy (RFS2/PFS2) for Arm A vs Arm C and Arm B vs Arm C	Time from randomization to recurrence/progression on next therapy (RFS2/PFS2)	Up to 49 months after first patient randomized

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Jia Fan, PhD, Liver Cancer Institute Zhongshan Hospital, Fudan University; Principal Investigator: Jennifer Knox, MD, Solid Tumor Medical Oncology Princess Margaret Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2019
• Primary Completion (Estimated): May 29, 2026
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: February 18, 2019
• First Submitted That Met QC Criteria: February 18, 2019
• First Posted (Actual): February 20, 2019

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Bevacizumab; Liver Cancer; Durvalumab; Early stage HCC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; durvalumab
• Other Study ID Numbers: D910DC00001; 2018-004105-85 (EudraCT Number); 2023-507689-26-00 (Registry Identifier: CTIS)

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 rerefer 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