NCT04605731

Durvalumab and Tremelimumab After Radioembolization for the Treatment of Unresectable, Locally Advanced Liver Cancer

A Phase Ib Study of Durvalumab (Medi4736) and Tremelimumab Following Radioembolization in Patients With Unresectable Locally Advanced Hepatocellular Carcinoma

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial investigates the side effects of durvalumab and tremelimumab after radioembolization (radiation particles against liver tumors) and to see how well they work in treating patients with liver cancer that cannot be removed by surgery (unresectable) and has spread to nearby tissues and lymph nodes (locally advanced). Durvalumab and tremelimumab are antibodies (proteins produced by the defense system of the body \[immune system\]) that have been made in the laboratory and may improve the ability of the immune system to detect and fight cancer.

Detailed description

PRIMARY OBJECTIVES: I. To establish the safety of durvalumab and tremelimumab following radioembolization with Yttrium-90 selective internal radiation (SIR)-spheres in patients with locally advanced hepatocellular carcinoma without extra-hepatic disease. II. If the combination of durvalumab and tremelimumab is deemed unsafe, to establish the safety of single agent durvalumab and explore all endpoints with durvalumab alone. III. To evaluate the overall response rate in patients treated with durvalumab and tremelimumab following radioembolization with Yttrium-90 SIR-Spheres using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, modified (m) RECIST and immune modified RECIST criteria. SECONDARY OBJECTIVES: I. To evaluate the rate of 6-month progression-free survival in patients treated with durvalumab and tremelimumab following radioembolization with Yttrium-90 SIR-spheres. II. To evaluate median progression-free survival and overall survival in patients treated with durvalumab and tremelimumab following radioembolization with Yttrium-90 SIR-spheres. EXPLORATORY OBJECTIVES: I. To explore the association of response and survival outcomes with PD-L1 expression of baseline tumor biopsies. II. To explore the association of response and survival outcomes with next generation sequencing results including tumor mutational burden of baseline tumor biopsies. III. To explore genomic alterations/evolutions in tumor tissue following Yttrium-90 SIR-spheres and durvalumab plus tremelimumab through comparison of baseline and post-combination immunotherapy treatment tumor biopsies. IV. To explore the association of response and survival outcomes with gene expression signatures. OUTLINE: Patients undergo standard of care radioembolization with Yttrium-90 SIR-spheres intra-arterially over 60-90 minutes on day -14. Patients then receive durvalumab intravenously (IV) over 1 hour and tremelimumab IV over 1 hour on day 1. Cycles with durvalumab repeat every 4 weeks for 12 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 90 days, and then every 12 weeks thereafter.

Conditions

• BCLC Stage B Hepatocellular Carcinoma
• BCLC Stage C Hepatocellular Carcinoma
• Locally Advanced 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	Durvalumab	Given IV
BIOLOGICAL	Tremelimumab	Given IV

Timeline

• Start date: 2021-08-03
• Primary completion: 2026-02-25
• Completion: 2026-02-25
• First posted: 2020-10-28
• Last updated: 2025-09-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study