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

Starting soon · Phase 2

Conditions studied: Locally Advanced Hepatocellular Carcinoma, Stage III Hepatocellular Carcinoma AJCC v8, Stage IV Hepatocellular Carcinoma AJCC v8, Unresectable Hepatocellular Carcinoma

In brief

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.

Key facts

Study ID

NCT07511504

Run by

OHSU Knight Cancer Institute

People needed

40

Starts

2026-04-02

Expected to finish

2027-08-01

Last updated by the study team

2026-04-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participant must provide written informed consent before any study-specific procedures or interventions are performed
• Participants aged ≥ 18 years
• Body weight > 30 kg
• Patients must have radiologically, or histologically or cytologically confirmed hepatocellular cancer that is not amenable to transplant or resection:
• Barcelona Clinic Liver Cancer Stage B or C
• Cirrhosis grade of Child-Pugh (CP) A or CP-B7 (excluding albumin-bilirubin [ALBI] grade 3)
• Fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible
• Disease must not be amenable to surgical resection, transplantation, or thermal ablation, or recurrent hepatocellular carcinoma (HCC) after a previous definitive therapy (surgery or thermoablative therapy)
• Venous invasion (portal, hepatic, biliary) and infiltrative growth pattern are eligible
• Eligible for Y-90 transarterial radioembolization (TARE) based on planning angiogram, with evidence of:
• ≥ 30% hepatic reserve (i.e., untreated background liver) AND
• Estimated lung exposure < 30 Gy/ treatment (or 50 Gy cumulative total)
• Patients with bi-lobar disease amenable to simultaneous or sequential TARE are eligible
• Eastern Cooperative Oncology Group (ECOG) 0 - 1 at enrollment
• Recovery to baseline or ≤ grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0) from toxicities related to any prior treatments, unless adverse events (AE[s]) are clinically non-significant and/or stable on supportive therapy
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L) (within 14 days before first dose of study treatment)
• White blood cell count ≥ 2500/μL (within 14 days before first dose of study treatment)
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L (1500/μL), without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection (within 14 days before first dose of study treatment)
• Platelet count ≥ 75 × 10\^9/L (≥ 75,000/μL), without transfusion within 2 weeks of screening laboratory sample collection (within 14 days before first dose of study treatment)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN) (within 14 days before first dose of study treatment)
• Alkaline phosphatase (ALP) ≤ 5 x ULN (within 14 days before first dose of study treatment)
• Total bilirubin ≤ 2 mg/dL (≤ 34.2 μmol/L) or < 2 x ULN, whichever is higher (within 14 days before first dose of study treatment)
• Serum albumin ≥ 2.8 g/dL (within 14 days before first dose of study treatment)
• International normalized ratio (INR) ≤ 1.7 x laboratory ULN (within 14 days before first dose of study treatment)
• Stable renal function defined as serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCL) ≥ 40mL/min (≥ 0.675mL/sec) using the Cockcroft-Gault equation (within 14 days before first dose of study treatment)

You may not qualify if…

• Another primary tumor
• Extrahepatic metastases
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
• Note: Eligible participants must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment.
• Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed
• Prior systemic therapy for HCC
• Prior Y-90 radioembolization
• Note: prior transarterial chemoembolization is permitted if > 6 months prior to enrollment
• Advanced liver disease with a CP-B7 (ALBI grade 3), CP-B8, CP-B9 or CP- C, or active gastrointestinal bleeding or encephalopathy or refractory ascites
• Radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Prior treatment with an anti-PD-1, anti-PD-L1, or anti-CTLA4 agent, or with an agent directed to another co-inhibitory T-cell receptor (e.g., TIGIT, LAG-3, TIM-3)
• Prior treatment with zanzalintinib, cabozantinib, or similar class of multitargeted Tyrosine Kinase Inhibitor (mTKI)
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment
• Participants cannot be on other forms of anti-cancer therapy at the same time, except as described within this protocol
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitors (e.g., rivaroxaban), or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low dose low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in participants without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen.
• Note: participants must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer
• Any complementary medications (e.g., herbal supplements or traditional medicines) to treat their HCC under study within 2 weeks before first dose of study treatment
• Participant has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Unstable of deteriorating cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, class 2 or higher, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (e.g., ventricular flutter, ventricular fibrillation, Torsades de pointes).
• Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
• Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other clinically significant arterial thrombotic and/or ischemic event within 6 months before first dose of study treatment.
• Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous events within 3 months before first dose of study treatment.

Where it is running

• OHSU Knight Cancer Institute — Portland, Oregon, United States

Full record on ClinicalTrials.gov

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