A Study Evaluating Atezolizumab, With or Without Bevacizumab, in Participants With Unresectable Hepatocellular Carcinoma and Child-pugh B7 and B8 Cirrhosis (Kirros)

May 29, 2026 updated by: Genentech, Inc.

A Phase II, Open-label, Multi-cohort, Multicenter Study in Patients With Unresectable Hepatocellular Carcinoma and Child-pugh B7 and B8 Cirrhosis

The purpose of this study is to assess the safety of atezolizumab and bevacizumab, or atezolizumab alone, as first-line treatment in participants with unresectable, locally advanced or metastatic hepatocellular carcinoma (HCC) with Child-pugh B7 or B8 cirrhosis.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase II, open-label, multicohort, multicenter study in participants with unresectable, locally advanced, or metastatic HCC who have Child-pugh B7 or B8 liver cirrhosis and have received no prior systemic therapy in this treatment setting. The study is designed to non-comparatively evaluate the safety of atezolizumab plus bevacizumab (Cohort A) or atezolizumab monotherapy (Cohort B) in this population.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Puerto Rico
      • Rio Piedras, Puerto Rico, 00935
        • Recruiting
        • Pan American Center for Oncology Trials, LLC
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • Recruiting
        • University of Arizona Cancer Center
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • UC San Diego Moores Cancer Center
      • Los Angeles, California, United States, 90089-5601
        • Recruiting
        • University of Southern California-Keck School of Medicine -1975 Zonal Ave
      • Newport Beach, California, United States, 92663
        • Recruiting
        • University of Southern California
      • Orange, California, United States, 92868
        • Completed
        • University of California Irvine Medical Center
      • Pasadena, California, United States, 91105-2561
        • Recruiting
        • California Liver Research Institute
      • Sacramento, California, United States, 95817
        • Completed
        • University of California Davis Medical Center
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford Health Care
      • Torrance, California, United States, 90502-2006
        • Recruiting
        • Harbor Ucla Medical Center
      • West Hollywood, California, United States, 90048-2422
        • Recruiting
        • Cedars Sinai Comprehensive Transplant Center
    • Colorado
      • Denver, Colorado, United States, 80218-1237
        • Recruiting
        • Rocky Mountain Cancer Centers (Williams) - USOR
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Recruiting
        • Hartford Healthcare Cancer Institute at Hartford Hospital
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20422-0001
        • Recruiting
        • Washington DC VA Medical Center
    • Florida
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Orlando Health Inc.
    • Illinois
      • Chicago, Illinois, United States, 60612-4795
        • Recruiting
        • University of Illinois Health Outpatient Care Center
      • Chicago, Illinois, United States, 60611-2908
        • Recruiting
        • Northwestern University
      • Chicago, Illinois, United States, 60637-1426
        • Recruiting
        • The Duchossois Center for Advanced Medicine
    • Kentucky
      • Lexington, Kentucky, United States, 40536-7001
        • Recruiting
        • University of Kentucky - Markey Cancer Center
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70808-4300
        • Recruiting
        • Our Lady of the Lake Cancer Institute
      • Baton Rouge, Louisiana, United States, 70805
        • Recruiting
        • LSU Health Baton Rouge
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02111
        • Recruiting
        • Tufts Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • Recruiting
        • Veterans Affairs Ann Arbor Healthcare System
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Health System
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Barbara Ann Karmanos Cancer Institute
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Recruiting
        • Saint Luke?s Hospital of Kansas City
    • New Jersey
      • Morristown, New Jersey, United States, 07962
        • Recruiting
        • MorristownMedicalCenter
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Rutgers Cancer Institute of New Jersey
      • Newark, New Jersey, United States, 07103
        • Recruiting
        • Rutgers Cancer Institute of New Jersey at University Hospital
    • New York
      • Mineola, New York, United States, 11501-4064
        • Recruiting
        • NYU Langone Hospital - Long Island
      • New Hyde Park, New York, United States, 11042-1118
        • Withdrawn
        • R.J. Zuckerberg Cancer Hospital/Northwell Health - BRANY - PPDS
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
      • New York, New York, United States, 10016-9451
        • Recruiting
        • NYU Langone Medical Center
      • The Bronx, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center
      • The Bronx, New York, United States, 10468-3904
        • Recruiting
        • James J Peters Veterans Administration Medical Center - NAVREF
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Levine Cancer Institute
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Withdrawn
        • University Hospitals Cleveland Medical Center
      • Dayton, Ohio, United States, 45428-9000
        • Recruiting
        • Dayton VA Medical Center - NAVREF - PPDS
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104-5020
        • Recruiting
        • The University of Oklahoma Health Sciences Center
    • Oregon
      • Hillsboro, Oregon, United States, 97124-5806
        • Recruiting
        • Kaiser Permanente Westside Medical Center
      • Portland, Oregon, United States, 97239-3011
        • Recruiting
        • OHSU Knight Cancer Institute Hematology Oncology
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Jefferson Health Honickman Center
      • Pittsburgh, Pennsylvania, United States, 15240
        • Completed
        • Veterans Affairs Pittsburgh Healthcare System - NAVREF - PPDS
    • Tennessee
      • Germantown, Tennessee, United States, 38138-1762
        • Active, not recruiting
        • The West Clinic (East Campus)
      • Nashville, Tennessee, United States, 37208-2918
        • Recruiting
        • Nashville General Hospital at Meharry
    • Texas
      • Dallas, Texas, United States, 75246-2008
        • Recruiting
        • Texas Oncology (Worth) - USOR
      • Dallas, Texas, United States, 75390-0001
        • Recruiting
        • University of Texas Southwestern Medical Center
      • Dallas, Texas, United States, 75203-1260
        • Recruiting
        • Liver Institute at Methodist Dallas
      • Dallas, Texas, United States, 75235
        • Recruiting
        • Moody Outpatient Center ? Parkland Health
      • Denison, Texas, United States, 75020-0084
        • Recruiting
        • Texas Oncology - Denison Cancer Center
      • Houston, Texas, United States, 77030
        • Recruiting
        • Houston Methodist Hospital
      • Houston, Texas, United States, 77025-1669
        • Recruiting
        • Kelsey Research Foundation
      • Houston, Texas, United States, 77030-4211
        • Recruiting
        • Michael E Debakey VA Medical Center - NAVREF - PPDS
    • Utah
      • Murray, Utah, United States, 84107-5741
        • Recruiting
        • Intermountain Healthcare
      • St. George, Utah, United States, 84790
        • Recruiting
        • Intermountain Cancer Center
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Completed
        • Inova Schar Cancer Institute
      • Newport News, Virginia, United States, 23602
        • Withdrawn
        • Maryview Hospital, Inc.
      • Richmond, Virginia, United States, 23298-5028
        • Recruiting
        • VCU Medical Center North Hospital
      • Richmond, Virginia, United States, 23226-1925
        • Recruiting
        • Bon Secours St. Mary's Hospital
    • Washington
      • Seattle, Washington, United States, 98101
        • Recruiting
        • Virginia Mason Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

General Inclusion Criteria:

  • Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants
  • Disease that is not amenable to curative surgical and/or locoregional therapies
  • No prior systemic treatment (including systemic investigational agents) for locally advanced or metastatic and/or unresectable HCC
  • Measurable disease (at least one untreated target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 7 days prior to initiation of study treatment
  • Child-pugh B7 or B8 cirrhosis at screening and within 7 days prior to study treatment
  • Adequate hematologic and end-organ function
  • Life expectancy of at least 12 weeks
  • Female participants of childbearing potential must be willing to avoid pregnancy and egg donation
  • Absolute neutrophil count ≥1.0 x 10^9 per liter (/L) (≥1000 per microliter [/μL]) without granulocyte colony-stimulating factor support
  • Platelet count ≥ 50 × 109/L (50,000/μL) without transfusion
  • Hemoglobin ≥ 80 grams per liter (g/L) (8 grams per deciliter [g/dL]) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × upper limit of normal (ULN)
  • Serum bilirubin ≤ 3 × ULN
  • Creatinine clearance ≥ 50 milliliters per minute (mL/min) (calculated using the Cockcroft-gault formula)
  • Serum albumin ≥ 20 g/L (2.0 g/dL) without transfusion in the prior 3 months
  • International normalized ratio (INR) ≤2.3

General Exclusion Criteria:

  • Pregnancy or breastfeeding
  • Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Treatment with locoregional therapy to liver within 28 days prior to initiation of study treatment, or non-recovery from side effects of any such procedure
  • Treatment with systemic immunostimulatory agents
  • Treatment with systemic immunosuppressive medication
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment
  • Inadequately controlled hypertension
  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Participants who have a known concurrent malignancy that is progressing or requires active treatment, who have not completely recovered from treatment, or who have a significant malignancy history that, in the opinion of the investigator, should preclude participation
  • Participants on preventative hormonal therapies (i.e., tamoxifen and other hormonal inhibitors) are not excluded
  • Known fibrolamellar HCC, sarcomatoid HCC, other rare HCC variant, or mixed cholangiocarcinoma and HCC
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
  • Prior allogeneic stem cell or solid organ transplantation
  • Actively listed for liver transplantation
  • Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV)
  • Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding
  • A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
  • Grade ≥3 hemorrhage or bleeding event within 6 months prior to initiation of study treatment
  • Hepatic encephalopathy is allowed if no active symptoms or stable within 3 months of study treatment
  • History, planned, or recommended placement of transjugular intrahepatic portosystemic shunt (TIPS) is excluded from Cohort A only. TIPS is acceptable in Cohort B
  • Diagnostic paracentesis is allowed. Therapeutic paracentesis: one large volume paracentesis prior to enrollment with diuretic controlled ascites is allowed.
  • Participants with ascites controlled on diuretics are allowed
  • History of spontaneous bacterial peritonitis within last 12 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort A: Atezolizumab+Bevacizumab
Participants will receive atezolizumab plus bevacizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator.
Drug: Atezolizumab
Atezolizumab will be administered at a dose of 1200 milligrams (mg) by intravenous (IV) infusion on Day 1 of each 21-day cycle.
Other Names:
  • Tecentriq; RO5541267
Drug: Bevacizumab
Bevacizumab will be administered at a dose of 15 milligrams per kilogram (mg/kg) by IV infusion on Day 1 of each 21-day cycle.
Other Names:
  • Avastin; RO4876646
Experimental: Cohort B: Atezolizumab
Participants will receive atezolizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator.
Drug: Atezolizumab
Atezolizumab will be administered at a dose of 1200 milligrams (mg) by intravenous (IV) infusion on Day 1 of each 21-day cycle.
Other Names:
  • Tecentriq; RO5541267

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Adverse Events (AEs)
Time Frame: Baseline through the end of the study (up to approximately 36 months)
An AE is any untoward medical occurrence in a participant or clinical study participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Severity is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) in Cohorts A and B.
Baseline through the end of the study (up to approximately 36 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Baseline up to approximately 36 months
Investigator-assessed confirmed ORR is defined as proportion of participants with a complete response/partial response (CR/PR) on two consecutive occasions ≥ 4 weeks apart with the use of Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) and hepatocellular carcinoma (HCC) modified Response Evaluation Criteria in Solid Tumors (mRECIST) in Cohorts A and B.
Baseline up to approximately 36 months
Duration of Response (DOR)
Time Frame: Baseline up to approximately 36 months
Investigator-assessed DOR is defined as the time from the first occurrence of a confirmed objective response to the time of disease progression, or death from any cause, whichever occurs first, with the use of RECIST v1.1 and HCC mRECIST in Cohorts A and B
Baseline up to approximately 36 months
Progression Free Survival (PFS)
Time Frame: Baseline up to approximately 36 months
Investigator-assessed PFS is defined as the time from treatment initiation to the first occurrence of disease progression with the use of RECIST v1.1 and HCC mRECIST, or death from any cause, whichever occurs first, in Cohorts A and B.
Baseline up to approximately 36 months
Overall Survival (OS)
Time Frame: Baseline up to approximately 36 months
OS is defined as the time from treatment initiation to the date of death due to any cause in Cohorts A and B.
Baseline up to approximately 36 months
Change From Baseline in EORTC QLQ-C30 Scores
Time Frame: Baseline up to approximately 36 months
The European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) is a validated, reliable self-reported measure. It consists of 30 questions that assess five aspects of participant functioning, three symptom scales, global health status and quality of life (QoL), and six single items with a recall period of the previous week. Scale scores can be obtained for the multi-item scales. The functioning and symptoms items are scored on a 4-point scale that ranges from "not at all" to "very much," and the global health status and QoL items are scored on a 7-point scale that ranges from "very poor" to "excellent."
Baseline up to approximately 36 months
Change From Baseline in EORTC QLQ-HCC18 Scores
Time Frame: Baseline up to approximately 36 months
The EORTC QLQ-HCC18 is a disease-specific measure designed for use along with the EORTC QLQ-C30 in patients with HCC. It contains six multi-item symptom scales, and two single-item scales for a total of 18 questions with a recall period the past week.
Baseline up to approximately 36 months
Change from baseline in PRO-CTCAE Scores
Time Frame: Baseline up to approximately 36 months
The Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a validated item bank that is used to characterize the presence, frequency of occurrence, severity, and/or degree of interference with daily function of 78 patient-reportable symptomatic treatment toxicities.
Baseline up to approximately 36 months
Percentage of Patient-Reported Overall Adverse Event Burden
Time Frame: Baseline up to approximately 36 months
The EORTC IL46 is a single question that assesses bother (burden) of treatment. It is rated on a scale from 1 to 4, ranging from "not at all" to "very much".
Baseline up to approximately 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genentech, Inc.

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 15, 2024

Primary Completion (Estimated)

July 30, 2027

Study Completion (Estimated)

December 30, 2027

Study Registration Dates

First Submitted

October 18, 2023

First Submitted That Met QC Criteria

October 18, 2023

First Posted (Actual)

October 24, 2023

Study Record Updates

Last Update Posted (Actual)

June 1, 2026

Last Update Submitted That Met QC Criteria

May 29, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ML44719

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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