NCT05776875

Atezolizumab and Bevacizumab in Combination With TACE for Patients With BCLC B HCC

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

There is an unmet need for patients with intermediate stage hepatocellular carcinoma (HCC). It is known that local tumor ablation can increase tumor immunogenicity by releasing tumor associated antigens, potentially increasing the response to immune therapy not just locally, but systemically. In addition, there is now positive data with immune therapy in advanced HCC, there is renewed interest in the combination of local therapy and systemic therapy in Barcelona Clinic Liver Clinic B (BCLC B) patients with systemic therapies other than sorafenib. Based on this data, the investigators plan to examine the atezolizumab and bevacizumab combination with Transarterial Chemoembolization (TACE) in patients with BCLC B HCC.

Detailed description

Targeting the Programmed Death-Ligand 1 (PD-L1) pathway with atezolizumab has demonstrated activity in patients with advanced malignancies who have failed standard-of-care therapies. Objective responses have been observed across a broad range of malignancies, including Non-Small-Cell Lung Cancer (NSCLC), urothelial carcinoma, Renal Cell Carcinoma (RCC), melanoma, colorectal cancer, head and neck cancer, gastric cancer, breast cancer, and sarcoma (see Atezolizumab Investigator's Brochure for detailed efficacy results). Atezolizumab has been generally well tolerated. Adverse events with potentially immune-related causes consistent with an immunotherapeutic agent, including rash, influenza-like illness endocrinopathies, hepatitis or transaminitis, pneumonitis colitis, and myasthenia gravis, have been observed (see Atezolizumab Investigator's Brochure for detailed safety results). To date, these events have been manageable with treatment or interruption of atezolizumab treatment. The combination of atezolizumab and bevacizumab in HCC has been well studied in both the phase 1 G030140 study and the phase 3 IMBrave150 study with response rates of 36% and 27% respectively. A phase 2 study of bevacizumab and TACE showed that the combination can be safely administered on the same day. Given concern for risk of bleeding with bevacizumab, all patients on these two studies had recent Endoscopic Gastroduodenoscopies (EGDs) and no patients with untreated varices were included. The risk of bleeding on both studies were reported as low, and risk of benefit was presented as outweighing risk. This trial will enroll patients with HCC who have BCLC B disease and are not candidates for curative treatment but are candidates for TACE. Typically, these patients would be treated with local treatment alone, but given the relatively poor prognosis and limited treatment options for these patients, this population is considered appropriate for trials of novel therapeutic candidates. The benefit-risk ratio for atezolizumab and bevacizumab in combination with TACE is expected to be acceptable in this setting.

Conditions

• Hepatocellular Carcinoma
• BCLC Stage B Hepatocellular Carcinoma

Interventions

Type	Name	Description
DRUG	Atezolizumab Injection	Atezolizumab is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), small cell lung cancer (SCLC), hepatocellular carcinoma, and alveolar soft part sarcoma It is a fully humanized, engineered monoclonal antibody of Immunoglobulin G1 (IgG1) isotype against the protein programmed cell death-ligand 1 (PD-L1).
DRUG	Bevacizumab	Bevacizumab, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma. In many of these diseases it is used as a first-line therapy. For age-related macular degeneration it is given by injection into the eye (intravitreal).
COMBINATION_PRODUCT	Transarterial chemoembolization	Transarterial chemoembolization (TACE) is a local therapy for HCC which induces tumor necrosis.

Timeline

• Start date: 2023-06-07
• Primary completion: 2024-12-05
• Completion: 2024-12-05
• First posted: 2023-03-20
• Last updated: 2025-01-15
• Results posted: 2025-01-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study