NCT05168163

Atezolizumab in Combination With a Multi-Kinase Inhibitor for the Treatment of Unresectable, Locally Advanced, or Metastatic Liver Cancer

A Phase II Randomized Study of Atezolizumab Plus Multi-Kinase Inhibitor Versus Multi-Kinase Inhibitor Alone in Subjects With Unresectable, Advanced Hepatocellular Carcinoma Who Previously Received Atezolizumab Plus Bevacizumab

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 122 (estimated)
• Sponsor: Academic and Community Cancer Research United · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests whether atezolizumab in combination with a multi-kinase inhibitor (cabozantinib or lenvatinib) compared to multi-kinase inhibitor alone in treating patients with liver cancer that cannot be removed by surgery (unresectable), has spread to has spread to nearby tissue or lymph nodes (locally advanced), or has spread to other places in the body (metastatic), for which the patient has received treatment in the past (previously treated). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib and lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab with cabozantinib or lenvatinib may kill more tumor cells in patients with liver cancer.

Detailed description

PRIMARY OBJECTIVE: I. To determine the progression-free and overall survival in subjects with advanced hepatocellular carcinoma who previously progressed on atezolizumab/bevacizumab who are treated using atezolizumab plus a multi-kinase inhibitor compared to multi-kinase inhibitor alone. SECONDARY OBJECTIVES: I. To determine the overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 response in subjects who are treated using atezolizumab plus a multi-kinase inhibitor compared to multi-kinase inhibitor alone. II. To determine the duration of response in subjects who are treated using atezolizumab plus a multi-kinase inhibitor compared to multi-kinase inhibitor alone. III. To determine the safety profile of adding atezolizumab to multi-kinase inhibitor in subjects who are treated using atezolizumab plus a multi-kinase inhibitor compared to multi-kinase inhibitor alone. EXPLORATORY OBJECTIVE: I. To explore for potential predictive biomarkers for response and resistance to anti-PD-L1 and/or multi-kinase inhibitor therapy in subject population. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1 and cabozantinib orally (PO) once daily (QD) or lenvatinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive cabozantinib PO QD or lenvatinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed-up every 9 weeks for up to 2 years.

Conditions

• Locally Advanced Hepatocellular Carcinoma
• Metastatic Hepatocellular Carcinoma
• Stage III Hepatocellular Carcinoma AJCC v8
• Stage IIIA Hepatocellular Carcinoma AJCC v8
• Stage IIIB Hepatocellular Carcinoma AJCC v8
• Stage IV Hepatocellular Carcinoma AJCC v8
• Stage IVA Hepatocellular Carcinoma AJCC v8
• Stage IVB Hepatocellular Carcinoma AJCC v8
• Unresectable Hepatocellular Carcinoma

Interventions

Type	Name	Description
BIOLOGICAL	Atezolizumab	Given IV
DRUG	Cabozantinib	Given PO
DRUG	Lenvatinib	Given PO

Timeline

• Start date: 2022-05-27
• Primary completion: 2025-12-31
• Completion: 2026-12-31
• First posted: 2021-12-23
• Last updated: 2025-09-16

Locations

16 sites across 1 country: United States

Regulatory

• FDA-regulated drug study