Atezolizumab, Bevacizumab, and Tocilizumab in Advanced Hepatocellular Carcinoma

Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age19+
SponsorCHA University

About this trial

This is a Phase 2, open-label, single-arm, multicenter study designed to evaluate the safety and efficacy of atezolizumab, bevacizumab, and tocilizumab in patients with locally advanced, metastatic, and/or unresectable hepatocellular carcinoma (HCC). Approximately 51 patients will be enrolled at 6 study sites and will receive combination therapy consisting of atezolizumab, bevacizumab, and tocilizumab. Patients assigned to the study will receive atezolizumab 1,200 mg intravenously and bevacizumab 15 mg/kg intravenously on Day 1 of each 21-day cycle, alongside tocilizumab 4 mg/kg intravenously on Day 1 of each 42-day cycle for up to 5 doses. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria are met. The study population includes adult patients with locally advanced, metastatic, and/or unresectable HCC who have received no prior systemic therapy for hepatocellular carcinoma. Eligible patients must have histologically, cytologically, or radiologically confirmed diagnosis, at least one measurable lesion according to RECIST version 1.1, Child-Pugh class A liver function, ECOG performance status 0 or 1, and adequate organ function. The primary objective is to assess the incidence of Grade 3 or higher immune-related adverse events (irAEs) occurring within 24 weeks after treatment initiation according to NCI CTCAE version 5.0. Secondary objectives include evaluation of objective response rate (ORR) and disease control rate (DCR) according to RECIST v1.1, progression-free survival, overall survival, and the rate of treatment discontinuation due to adverse events. Safety evaluations will include assessment of adverse events, serious adverse events, laboratory parameters, vital signs, and other clinical assessments. Exploratory objectives include evaluation of the correlation between treatment response and serum inflammatory markers (such as IL-6 and CRP) and immune cell profiles using blood samples collected at protocol-defined intervals. Tumor assessments will be performed at protocol-defined intervals using radiologic imaging every 6 weeks from Cycle 1 Day 1 up to Week 54, and every 9 weeks thereafter. The primary efficacy analysis will be based on the Full Analysis Set according to RECIST v1.1. This study is intended to evaluate the clinical activity and safety profile of prophylactic tocilizumab in combination with atezolizumab and bevacizumab in this patient population and to generate data to inform future clinical development.

Eligibility criteria

Qualifiers

Histologically, cytologically, or radiologically confirmed diagnosis of locally advanced, metastatic, and/or unresectable hepatocellular carcinoma (HCC).

Age ≥19 years at the time of signing the informed consent form (ICF).

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study drug.

Child-Pugh class A (score 5-6) within 7 days prior to the first dose of study drug.

Disqualifiers

Prior systemic therapy for locally advanced, metastatic, and/or unresectable hepatocellular carcinoma, including chemotherapy, biologic therapy, immunotherapy, hormonal therapy, or investigational agents.

Presence of multiple primary malignancies.

Known fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, or mixed hepatocellular-cholangiocarcinoma.

Untreated or incompletely treated esophageal or gastric varices with bleeding or high risk of bleeding: Patients must undergo esophagogastroduodenoscopy (EGD) prior to enrollment, and all varices must be evaluated and treated according to institutional standard of care. If evaluation has been performed within 6 months prior to the first dose of study drug, repeat evaluation is not required.

Trial design

Treatments tested in this trial

  • Atezolizumab
  • Bevacizumab
  • Tocilizumab

Treatment groups

51 Participants
are divided into 1 treatment group

Sponsors and collaborators