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

Study Overview
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Brief Summary
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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.

Detailed Description
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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 125 participants with unresectable but amenable to locoregional therapy HCC eligible for embolization will be enrolled in the study at approximately 20 sites in the US to treat approximately 100 participants.

Official Title
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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

Conditions
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Hepatocellular Carcinoma (HCC)

Intervention / Treatment
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* Drug: Durvalumab
* Drug: Bevacizumab
* Procedure: Transarterial Radioembolization (TARE)


Participation Criteria
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Eligibility Criteria
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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 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 or transplantation or curative ablation. 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TARE, Durvalumab, Bevacizumab, Liver Cancer, Y90