A US Study to Evaluate Transarterial Radioembolization (TARE) in Combination With Durvalumab and Bevacizumab Therapy in People With Unresectable Hepatocellular Carcinoma Amenable to TARE (EMERALD-Y90)

Phase II Single-Arm Study of Durvalumab and Bevacizumab Following Transarterial Radioembolization Using Yttrium-90 Glass Microspheres (TheraSphere™) in Unresectable Hepatocellular Carcinoma Amenable to Locoregional Therapy

The purpose of this study is to measure the efficacy and safety of durvalumab intravenous (IV) solution plus bevacizumab IV solution after transarterial radioembolization (Yttrium 90 glass microspheres TARE) in participants with unresectable hepatocellular carcinoma (HCC) amenable to embolization.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Drug: Durvalumab; Drug: Bevacizumab; Procedure: Transarterial Radioembolization (TARE)

Detailed Description

A Phase II single-arm study conducted in participants with unresectable Hepatocellular carcinoma (HCC) eligible for embolization and not eligible for or who have declined treatment with resection and/or ablation or liver transplant.

Participants with previous Transarterial Chemoembolization (TACE) or TARE associated with the curative setting are permitted with a 6-month washout.

Approximately 120 participants with unresectable but amenable to locoregional therapy HCC eligible for embolization will be screened in the study at approximately 20 sites in the US to enroll approximately 60 participants.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • Florida
    • Gainesville, Florida, United States, 32608
      • Research Site
    • Orlando, Florida, United States, 32804
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
    • Atlanta, Georgia, United States, 30342
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Research Site
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Research Site
  • New Jersey
    • Trenton, New Jersey, United States, 08690
      • Research Site
  • New York
    • Buffalo, New York, United States, 14263
      • Research Site
    • New York, New York, United States, 10029
      • Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98195
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Research Site
    • Milwaukee, Wisconsin, United States, 53215
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants with confirmed unresectable HCC
• Participants with Lung dose threshold for Yttrium 90 glass microspheres of 30 Gy (equal or less than 30 Gy per treatment for glass) and an estimated Future liver remnant volume (FLRV) ≥ 30% of whole liver volume.
• Participants with more than 1 prior embolization are permitted if more than 12 months ago, for a different primary lesion, and FLR > 30%.
• Participants with no evidence of extrahepatic disease on any available imaging
• Participants with one or more measurable lesions, unilobar disease for participants with segmental or right anterior/posterior portal vein invasion (Vp1/Vp2) and eligible for Yttrium 90 glass microspheres TARE.
• Participants having Child-Pugh score class A.
• Participants having ECOG performance status of 0 or 1 at enrollment
• Adequate organ and marrow function

Exclusion Criteria:

• Disease amenable to curative surgery, ablation or transplantation. Transplant patients are considered eligible if outside of Milan criteria and not currently listed for transplant.
• Participants co-infected with HBV and HDV
• Any history of nephrotic or nephritic syndrome.
• Clinically significant (eg, active) cardiovascular disease
• Participants with uncontrolled hypertension
• History of hepatic encephalopathy
• Known hereditary predisposition to bleeding or thrombosis; any prior or current evidence of bleeding diathesis.
• Receipt of more than 1 prior embolization (TACE or TARE) treatment/procedure
• Participant has received any prior anticancer systemic therapy for unresectable HCC.
• History of arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to enrollment.
• History of abdominal fistula or gastrointestinal (GI) perforation, non-healed gastric ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab; Participants will undergo Yttrium 90 glass microspheres TARE according to the dosimetry recommendation.	Drug: Durvalumab; Durvalumab IV (intravenous); Other Names: MEDI4736, IMFINZI; Drug: Bevacizumab; Bevacizumab IV (intravenous); Other Names: AVASTIN, ZIRABEV; Procedure: Transarterial Radioembolization (TARE); Yttrium 90 glass microspheres will be administered; Other Names: TheraSphere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is defined as the time from Day 1 (day of TARE) until the date of progressive disease per modified Response Evaluation Criteria in Solid Tumors (mRECIST), as assessed by the investigator, or death due to any cause. It is measured to assess the efficacy of TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy.	From Day 1 until date of progressive disease or death [Approximately 3 years]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse events (AEs)	To assess the safety of the sequence of TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy	From Screening (Day -28 to Day 1) until 90 days after the last dose of study drug
Objective Response Rate (ORR)	ORR is defined as the proportion of participants who have a confirmed complete response or partial response, as determined by the investigator per mRECIST. It is assessed after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy.	From Day 1 until progression, or the last evaluable assessment in the absence of progression (Approximately 3 years)
Overall Survival (OS)	OS is defined as the time from the start of TARE until the date of death due to any cause. It is assessed after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy.	Day 1 to 18 months or until death (Approximately 3 years)
Duration of Response (DoR)	DoR is defined as the time from the date of first documented response (that is subsequently confirmed) until the date of documented progression per mRECIST as assessed by the investigator, or death due to any cause. It is assessed after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy.	Time from first documented response until documented progression (Approximately 3 years)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: September 11, 2023
• First Submitted That Met QC Criteria: September 11, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Bevacizumab; Liver Cancer; Durvalumab; TARE; Y90
• 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: D933GC00002

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.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• 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 deidentified 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: Yes