NCT07042919

Zanzalintinib in Second Line and Beyond for the Treatment of Advanced Liver Cancer

A Phase Ib/II Study of Zanzalintinib in Second Line and Beyond for the Treatment of Advanced Hepatocellular Carcinoma

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 53 (estimated)
• Sponsor: Northwestern University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib/II trial tests the safety, side effects, and best dose of zanzalintinib and how well it works in treating patients with hepatocellular (liver) cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Zanzalintinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply, which may help keep tumor cells from growing. Giving zanzalintinib may be safe, tolerable, and/or effective in treating patients with advanced liver cancer.

Detailed description

PRIMARY OBJECTIVE: I. To assess the safety, tolerability, and dose limiting toxicity (DLT) in patients with advanced hepatocellular carcinoma (aHCC, Child-Pugh class A and B cirrhosis) and the determination of the recommended phase II dose (RP2D) with zanzalintinib. (Phase Ib dose escalation only) SECONDARY OBJECTIVES: I. Assess the proportion of aHCC zanzalintinib treated patients that are alive and median progression-free survival (PFS) of treatment. (Phase Ib and Phase II) II. Assess median overall survival (OS) in aHCC zanzalintinib treated patients. (Phase Ib and Phase II) III. Assess the proportion of aHCC zanzalintinib treated patients that have an objective response to treatment by imaging. EXPLORATORY (CORRELATIVE) OBJECTIVE: I. Assess correlatives and the pharmacokinetics (PK) profile by biomarker assessment during treatment of aHCC patients with zanzalintinib. OUTLINE: This is a phase Ib dose-escalation study followed by a phase II dose-expansion study. Patients receive zanzalintinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at baseline and urine and blood sample collection and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for up to 1 year.

Conditions

• Advanced Hepatocellular Carcinoma
• Cirrhosis
• Stage III Hepatocellular Carcinoma AJCC v8
• Stage IV Hepatocellular Carcinoma AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo urine and blood sample collection
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Echocardiography Test	Undergo ECHO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
DRUG	Zanzalintinib	Given PO

Timeline

• Start date: 2026-03-04
• Primary completion: 2029-03-04
• Completion: 2031-03-04
• First posted: 2025-06-29
• Last updated: 2025-06-29

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study