CTLA-4 /PD-L1 Blockade Following Transarterial Chemoembolization (DEB-TACE) in Patients With Intermediate Stage of HCC (Hepatocellular Carcinoma) Using Durvalumab and Tremelimumab

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of immunotherapy durvalumab and tremelimumab combined with DEB-TACE in patients with Hepatocellular Carcinoma.

Official Title
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The Effect of CTLA-4/PD-L1 Blockade Following Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) in Patients With Intermediate Stage of HCC Using Durvalumab (MEDI4736) and Tremelimumab

Conditions
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Intermediate Stage of Hepatocellular Carcinoma, Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Durvalumab
* Drug: Tremelimumab (Cohort A dose)
* Drug: Tremelimumab (Cohort B dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form Age ≥18 years. Newly diagnosed with hepatocellular carcinoma Have measurable disease Have disease that responds to DEB-TACE Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Body weight >30 kg Evidence of clinical or radiographic ascites with a score < 7 Patients must have adequate organ function defined by study-specified laboratory tests. Evidence of post-menopausal status or negative pregnancy test Willing and able to comply with study procedures Willing to undergo a liver biopsy Exclusion Criteria: Anyone involved with the planning and/or conduct of the study. Has participated in another investigational study during the last 6 months. Any concurrent anticancer therapy or received therapy ≤30 days prior to study. Major surgical procedure at the time of study enrollment or within 28 days prior to the first dose of IP. Have a diffuse HCC (Hepatocellular Carcinoma), vascular invasion or extrahepatic tumor. Main portal vein thrombosis present on imaging. History of hepatic encephalopathy within past 12 months or require medications to prevent or control encephalopathy. Ascites within 6 weeks prior to study treatment. Any contraindications for embolization. Has an active infection such as TB, HIV, hepatitis B or C. History of another primary malignancy. History of leptomeningeal carcinomatosis. History of active primary immunodeficiency. Any unresolved toxicities from previous anticancer therapy. Grade ≥2 neuropathy. History of bleeding disorder. History or current use of immunosuppressive medications within 14 days prior to study medications. Has an active known or suspected autoimmune disease. Patients with hypothyroidism. Any active skin conditions. History of allogenic organ transplantation. Significant heart disease. Patients weighing < 30 kg. Patients with celiac disease not controlled by diet alone. Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Have received a live vaccine within 30 days prior to study drug. Woman who are pregnant or breastfeeding. Known allergy or hypersensitivity to the study drug. Have received durvalumab, tremelimumab, anti-PD-1, anti-PD-L1 or anti-CTLA-4 in a prior study. Unwilling or unable to follow the study schedule for any reason.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Durvalumab in combination with Tremelimumab (Cohort A dose)<br>Starting at week 2, after initial DEB-TACE treatment, patients will receive Durvalumab in combination with tremelimumab, as specified per protocol (Cohort A dose). Treatment will continue for up to 12 months, while receiving DEB-TACE. Repeat DEB-TACE will be provided Q8W if there is residual tumor that can be targeted. | Drug: Durvalumab<br>* Durvalumab IV<br>* Other names: MEDI4736;Drug: Tremelimumab (Cohort A dose)<br>* Tremelimumab IV<br>* Other names: CP-675,206;|
| Experimental: Durvalumab in combination with Tremelimumab (Cohort B dose)<br>Starting at week 2, after initial DEB-TACE treatment, patients will receive Durvalumab in combination with tremelimumab as specified per protocol (Cohort B dose). Treatment will continue for up to 12 months, while receiving DEB-TACE. Repeat DEB-TACE will be provided Q8W if there is residual tumor that can be targeted. | Drug: Durvalumab<br>* Durvalumab IV<br>* Other names: MEDI4736;Drug: Tremelimumab (Cohort B dose)<br>* Tremelimumab IV<br>* Other names: CP-675,206;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. | Proportion of participants with reduction in tumor burden as defined by mRECIST criteria. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | Number of months until disease progression or death | 2 years | 
| Tumor response as determined by number of participants with partial (PR) or complete response (CR) as defined by mRECIST criteria | PR is defined as >=30% reduction in size of target lesions, whereas CR is defined as disappearance of all target lesions | 2 years | 
| Overall Survival (OS) | Number of months until death from any-cause | 2 years | 
| Number of participants experiencing study drug-related toxicities | Number of participants experiencing drug-related adverse events >= Grade 3 or higher as defined by CTCAE v5.0 | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC, Durvalumab, Tremelimumab, Immunotherapy, PD-L1, Antibodies, Hepatocellular Carcinoma, CTLA-4, DEB-TACE