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.

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.