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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma; Intermediate Stage of Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Durvalumab; Drug: Tremelimumab

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed informed consent form
• Age ≥18 years.
• Patients with diagnosis of HCC either by high-resolution imaging (triple-phase CT or MRI) and/or by tumor biopsy.
• Patient is not on systemic treatment for diagnosis of HCC
• HCC meeting Barcelona Clinic Liver Cancer (BCLC) stage B (intermediate stage), with measurable lesions on CT or MRI and without extrahepatic spread
• Have measurable disease
• Have disease that responds to DEB-TACE
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Child-Pugh Score of A or early B (score ≤8) without clinically significant ascites
• Body weight >30 kg
• 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 study drug.
• Have a vascular invasion or extrahepatic tumor.
• Main portal vein thrombosis present on imaging.
• Uncontrolled hepatic encephalopathy at time of enrollment. - Ascites within 6 weeks prior to study treatment.
• Any contraindications for embolization.
• Has an active infection such as Tuberculosis, HIV, hepatitis B or C.
• History of another primary malignancy or myeloproliferative disorder.
• History of leptomeningeal carcinomatosis.
• History of active primary immunodeficiency.
• Any unresolved toxicities from previous anticancer therapy.
• Active or prior documented GI bleeding due to ulcer or esophageal varices bleeding within 6 months.
• History or current use of immunosuppressive medications within 14 days prior to study medications.
• Major surgical procedure within 28 days prior to the first dose of IP.
• 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.

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: Durvalumab in combination with Tremelimumab; Drug: Durvalumab 1500mg IV + Tremelimumab 300 mg IV , single infusion about 2 weeks after first DEB-TACE procedure. Drug: Durvalumab (monotherapy) 1500 mg IV infusion every 4 weeks, for maximum 13 doses/cycles.	Drug: Durvalumab; Durvalumab 1500mg IV every 4 weeks for up to a maximum of 13 cycles (about 12 months) or until confirmed disease progression.; Other Names: MEDI4736; Drug: Tremelimumab; Tremelimumab 300 mg IV in combination with Durvalumab 1500mg about 2 weeks after their first DEB-TACE.; Other Names: CP-675,206

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on mRECIST criteria. CR = Disappearance of any intratumoral arterial enhancement in all target lesions, PR = At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions.	up to 26 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug-related Toxicity	Number of participants experiencing drug-related adverse events (AE) Grade 3 or higher as defined by CTCAE v5.0	up to 16 months
Progression Free Survival (PFS)	Progression free survival is defined as the time from start of the treatment until the documentation of disease progression according to mRECIST or death due to any cause, whichever occurs first. Estimation based on the Kaplan-Meier curve.	up to 58 months
Overall Survival (OS)	Overall survival is the time from the start of first dose of study drug to death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.	up to 58 months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Ana De Jesus-Acosta, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2019
• Primary Completion (Actual): August 20, 2024
• Study Completion (Actual): August 20, 2024

Study Registration Dates

• First Submitted: August 15, 2018
• First Submitted That Met QC Criteria: August 16, 2018
• First Posted (Actual): August 20, 2018

Study Record Updates

• Last Update Posted (Actual): August 17, 2025
• Last Update Submitted That Met QC Criteria: July 30, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; HCC; Immunotherapy; PD-L1; Antibodies; Durvalumab; CTLA-4; Tremelimumab; DEB-TACE
• 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; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents, Immunological; Antineoplastic Agents; Durvalumab; Tremelimumab
• Other Study ID Numbers: J18118; IRB00179347 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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