NCT07511504

Y-90 Radioembolization, Durvalumab, Tremelimumab, and Zanzalintinib for the Treatment of Unresectable and Locally-Advanced Hepatocellular Carcinoma

A Phase II Study to Evaluate the Efficacy and Safety of Y-90, Durvalumab, Tremelimumab, and Zanzalintinib in Patients With Unresectable and Locally-Advanced Hepatocellular Carcinoma

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: OHSU Knight Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests how well giving Y-90 radioembolization, durvalumab, tremelimumab and zanzalintinib works for the treatment of hepatocellular carcinoma that cannot be removed by surgery (unresectable) and that has spread to nearby tissue or lymph nodes (locally advanced). Y-90 radioembolization is a therapy that injects radioactive particles directly into an artery that feeds liver tumors to cut off their blood supply. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Zanzalintinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving Y-90 radioembolization, durvalumab, tremelimumab and zanzalintinib may be effective for treating unresectable and locally-advanced hepatocellular carcinoma.

Detailed description

PRIMARY OBJECTIVE: I. To assess proportion of participants that are progression-free at 6 months. SECONDARY OBJECTIVES: I. To assess safety of study intervention. II. To estimate objective response rate (ORR) for study intervention. III. To estimate disease control rate (DCR) for study intervention. IV. To estimate time to disease progression (TTP) for study intervention. V. To estimate progression-free survival. VI. To estimate overall survival (OS) for study intervention. EXPLORATORY OBJECTIVE: I. To evaluate therapy induced changes in the tumor and tumor immune microenvironments. OUTLINE: CYCLE 1: Patients receive tremelimumab intravenously (IV) and durvalumab IV, over 60 minutes, on day 1. 7-14 days later patients undergo transarterial radioembolization with yttrium (Y)-90 in the absence of disease progression or unacceptable toxicity. 7 days to 12 weeks later patients proceed to cycle 2. CYCLE 2-12: Patients receive durvalumab IV, over 30-60 minutes, on day 1 and zanzalintinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo angiogram during screening and undergo single photon emission computed tomography (SPECT), computed tomography (CT) scan or magnetic resonance imaging (MRI), and blood and urine sample collection throughout the study. Patients optionally undergo tumor biopsy throughout the study. After completion of study treatment, patients are followed up at 100 days and every 6 months for 1 year.

Conditions

• Locally Advanced Hepatocellular Carcinoma
• Stage III Hepatocellular Carcinoma AJCC v8
• Stage IV Hepatocellular Carcinoma AJCC v8
• Unresectable Hepatocellular Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Angiogram	Undergo angiogram
PROCEDURE	Biopsy Procedure	Undergo tumor biopsy
PROCEDURE	Biospecimen Collection	Undergo blood and urine sample collection
PROCEDURE	Computed Tomography	Undergo CT scan
BIOLOGICAL	Durvalumab	Given IV
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Single Photon Emission Computed Tomography	Undergo SPECT
BIOLOGICAL	Tremelimumab	Given IV
PROCEDURE	Yttrium-90 Microsphere Radioembolization	Given via transartieral radioembolization procedure
DRUG	Zanzalintinib	Given PO

Timeline

• Start date: 2026-04-02
• Primary completion: 2027-08-01
• Completion: 2027-08-01
• First posted: 2026-04-06
• Last updated: 2026-04-06

Locations

1 site across 1 country: United States