Maintenance Zanzalintinib and Durvalumab in Participants With Advanced Hepatocellular Cancer

NCT07226063 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CASE11225
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatocellular Carcinoma; Liver Cancer

Keywords

Zanzalintinib; Durvalumab

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) at 16 weeks

  Progression-Free Survival (PFS) is defined as the duration of time from start of treatment to time of disease progression or death, whichever occurs first.

  Week 16

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Up to 2 years

• Safety and tolerability, as measured by incidence and severity of adverse events

  Up to 2 years

• Overall Survival (OS)

  Until death, up to 2 years

• Clinical benefit rate

  Up to 2 years

• Progression-Free Survival (PFS)

  Up to 2 years

Study Arms (1)

Durvalumab + zanzalintinib

EXPERIMENTAL

Participants will receive treatment regimen of durvalumab and zanzalintinib. Each treatment cycle is 28 days. Participants will continue to receive treatment until disease progression, death, or other reasons for withdrawal.

Drug: Durvalumab; Drug: Zanzalintinib

Interventions

Durvalumab DRUG

Participants will receive 1500 mg durvalumab through intravenous (IV) administration over a period of 60 minutes on Day 1 of each 28-day cycle.

Durvalumab + zanzalintinib

Zanzalintinib DRUG

Participants will receive 60 mg durvalumab orally on Days 1-28 of each 28-day cycle.

Durvalumab + zanzalintinib

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• Amit Mahipal: lead
• Exelixis: collaborator

Study Sites (1)

University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Amit Mahipal, MD, MBBS

  Case Comprehensive Cancer Center, University Hospitals

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amit Mahipal, MD, MBBS

CONTACT

216-844-3951; Amit.Mahipal@UHhospitals.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 6, 2025
• First Posted: November 10, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)