Maintenance Zanzalintinib and Durvalumab in Participants With Advanced Hepatocellular Cancer

Starting soon · Phase 2

Conditions studied: Hepatocellular Carcinoma, Liver Cancer

In brief

This research study is for people who were treated with tremelimumab and durvalumab for advanced liver cancer and who are currently receiving durvalumab. Participants in this study will receive a drug called zanzalintinib. They will also continue receiving durvalumab. Studies have shown that patients with advanced liver cancer who had tremelimumab and durvalumab may benefit from taking zanzalintinib while they are taking durvalumab. Zanzalintinib is an investigational drug. This means it has not been approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with advanced liver cancer. Durvalumab is approved by the FDA for patients with advanced liver cancer. The purpose of this study is to find out if taking zanzalintinib with durvalumab will improve how long people with advanced liver cancer will live.

Key facts

Study ID

NCT07226063

Run by

Amit Mahipal

People needed

16

Starts

2026-05-01

Expected to finish

2028-08-01

Last updated by the study team

2026-05-05

Who can join

Age: 19 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must have radiographically or histologically or cytologically confirmed hepatocellular cancer. Participants must have advanced cancer (metastatic or unresectable) requiring systemic therapy.
• Participants must be treated with tremelimumab plus durvalumab and have stable disease or response to therapy. Participants must have received 2 to 5 doses of durvalumab prior to starting treatment on the clinical trial.
• Age >18 years. Because no dosing or adverse event data are currently available on the use of durvalumab in combination with zanzalintinib in participants ≤18 years of age, children are excluded from this study.
• ECOG Performance status 0-2.
• Participants must have normal organ and marrow function as defined below based upon meeting all the following laboratory criteria within 14 days before first dose of study treatment:
• Absolute neutrophil count ≥ 1,500/mcL 1,500/mcL (without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection)
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L) without transfusion within 2 weeks prior to screening laboratory sample collection.
• Platelet count ≥ 75,000/mcL
• Total bilirubin < 2.0 mg/dL or <2x upper limit of normal (ULN) whichever is higher
• AST (SGOT) ≤ 5 X institutional upper limit of normal
• ALT (SGPT) ≤ 5 X institutional upper limit of normal
• Creatinine clearance ≥ 40 mL/min (≥ 0.67 mL/sec) using the Cockcroft Gault equation
• International Normalized Ratio (INR) ≤ 1.7 and/or activated partial thromboplastin time (aPTT) ≤ 1.2 x ULN.
• Serum albumin at least 2.5g/dL for Child-Pugh A
• Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine
• Child Pugh Score A 5-6
• Participants must have the ability to understand and the willingness to sign a written informed consent document.
• At least one index lesion that is measurable based on RECIST 1.1.
• Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from AEs, including immune-related adverse events (irAEs), related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (eg, physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, ≤ Grade 2 fatigue, ≤ Grade 2 hypomagnesemia, ≤ Grade 2 neuropathy are permitted)
• Sexually active fertile participants and their partners must agree to use highly effective method of contraception during the course of the study and for the following durations after the last dose of zanzalintinib or duvalumab whichever was administered later. An additional contraceptive method, such as a barrier method (eg, condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.
• through 186 days after the last dose of zanzalintinib or durvalumab for women of childbearing potential (WOCBP) or through 96 days after the last dose of zanzalintinib or durvalumab for men
• Female participants of childbearing potential must not be pregnant at screening. Female participants are considered to be of childbearing potential unless one of the following criteria is met: permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes. In addition, females < 55 years-of-age must have a serum follicle stimulating hormone [FSH] level > 40 mIU/mL to confirm menopause). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.

You may not qualify if…

• Inability to swallow tablets or ingest a suspension either orally or by a nasogastric (NG) or gastrostomy (PEG) tube.
• Participants receiving any other investigational agents concurrently for cancer treatment.
• Participants with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of solid organ or allogeneic stem cell transplant.
• Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. This includes unstable or 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 (eg, 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, 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.
• Note: Participants with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and 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 who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the Principal Investigator.
• Prior history of myocarditis.
• Gastrointestinal (GI) disorders associated with a high risk of perforation or fistula formation:
• Tumors invading the GI-tract from external viscera
• Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis
• Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months before first dose unless cause of obstruction is definitively managed and participant is asymptomatic
• Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
• Known gastric or esophageal varices
• Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks
• Active infection requiring systemic treatment. Note: Prophylactic antimicrobial treatments (antibiotics, antimycotic, antiviral) are allowed.
• Known infection with acute or chronic hepatitis B or C, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness except for participants meeting all of the following criteria: (1) on stable anti-retroviral therapy; (2) CD4+ T cell count ≥ 200/µL; and (3) an undetectable viral load. Note: HIV testing will be performed at screening if and as required by local regulation. Note: To be eligible, participants taking CYP inhibitors (eg, zidovudine, ritonavir, cobicistat, didanosine) or CYP3 inducers (efavirenz) must change to a different regimen not including these drugs 7 days prior to initiation of study treatment. Anti-retroviral therapies (ART) must have been received for at least 4 weeks prior to the first dose. Note: CD4+ T cell counts, and viral load are monitored per standard of care by the local health care provider. Following illnesses/conditions are also excluded
• Serious non-healing wound/ulcer/bone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions.
• Malabsorption syndrome.
• Pharmacologically uncompensated, symptomatic hypothyroidism.
• Requirement for hemodialysis or peritoneal dialysis
• Prior treatment with tyrosine kinase inhibitors for HCC

Where it is running

• University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center — Cleveland, Ohio, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.