A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma

NCT ID: NCT05908786

Last Updated: 2025-12-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-05
• Study Completion Date: 2025-11-13

Brief Summary

This is a Phase Ib/II, open-label, multicenter, randomized platform study to evaluate neoadjuvant immunotherapy combinations in participants with resectable HCC. The study is designed with the flexibility to open new treatment arms as new agents become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the participant population.

Conditions

Carcinoma, Hepatocellular

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atezo + Bev

Participants in the atezolizumab plus bevacizumab (Atezo + Bev) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.

Atezo + Bev +Tira

Participants in the atezolizumab plus bevacizumab plus tiragolumab (Atezo + Bev +Tira) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.

Tiragolumab

Intervention Type: DRUG

Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1.

Tobe + Bev

Participants in the Tobemstomig + Bev arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.

Enrollment is closed.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.

Tobemstomig

Intervention Type: DRUG

Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1

Interventions

Atezolizumab

Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.

Intervention Type: DRUG

Bevacizumab

Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.

Intervention Type: DRUG

Tiragolumab

Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1.

Intervention Type: DRUG

Tobemstomig

Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1

Intervention Type: DRUG

Other Intervention Names

Tecentriq; Avastin; RO7247669

Eligibility Criteria

Inclusion Criteria

• Diagnosis of HCC confirmed either histologically or clinically according to AASLD criteria for patients with cirrhosis. For participants without cirrhosis, histological confirmation is mandatory.
• HCC that is amenable to R0 surgical resection with curative intent in the opinion of the surgeons and oncologists or hepatologists involved in the care of the participant. Patients presenting with resectable HCC within or beyond Milan criteria (without extrahepatic spread or macrovascular invasion) are eligible.
• Measurable disease (at least one target lesion) according to RECIST v1.1 as determined by the investigator
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization
• Child-Pugh Class A within 7 days prior to randomization
• Negative HIV test at screening
• No prior locoregional or systemic treatment for HCC
• Adequate hematologic and end-organ function
• Documented virology status of hepatitis
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm

Exclusion Criteria

• Presence of extrahepatic disease or macrovascular invasion
• Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC, or other rare variants of HCC
• History of hepatic encephalopathy if clinically significant within one year prior to initiation of study treatment
• Moderate or severe ascites
• Active co-infection with HBV and HCV
• Known active co-infection with HBV and hepatitis D viral infection
• Prior treatment with CD137 agonists or immune checkpoint inhibitors, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• 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
• Inadequately controlled hypertension
• History of hypertensive crisis or hypertensive encephalopathy
• Significant vascular disease within 6 months prior to initiation of study treatment
• History of hemoptysis within 1 month prior to initiation of study treatment
• Evidence of bleeding diathesis or significant coagulopathy
• Current or recent (<= 10 days prior to initiation of study treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes
• History of abdominal or tracheoesophageal fistula, GI perforation or intra-abdominal abscesses within 6 months prior to initiation of study treatment
• History of intestinal obstruction and/or clinical sign or symptoms of GI obstruction
• Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
• Grade >= proteinuria
• Major surgical procedure, open biopsy, or significant traumatic injury, or abdominal surgery, interventions or traumatic injuries, or anticipation of need of major surgical procedure other than potentially curative liver resection
• Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)
• Serious infection requiring oral or IV antibiotics and/or hospitalization
• Active tuberculosis

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

University of Southern California (USC)

Los Angeles, California, United States

University of California Los Angeles (UCLA) - Cancer Care - Santa Monica

Santa Monica, California, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center - Main Campus

Detroit, Michigan, United States

Columbia University Medical Center

New York, New York, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Klinikum Klagenfurt am Wörthersee

Klagenfurt, , Austria

Wiener Gesundheitsverbund, Klinik Favoriten

Vienna, , Austria

Department of Internal Medicine III AKH and Medical University of Vienna

Vienna, , Austria

Centre Georges Francois Leclerc (CGFL)

Dijon, , France

Centre Eugene Marquis (CEM)

Rennes, , France

Assistance Publique-Hopitaux de Paris

Villejuif, , France

Gustave Roussy

Villejuif, , France

University Essen

Essen, , Germany

Universitaets Klinikum Frankfurt - Zentrum der Inneren Medizin

Frankfurt, , Germany

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

Mainz, , Germany

Auckland District Health Board (ADHB)

Auckland, , New Zealand

CHA Bundang Medical Center

Seongnam-si, Gyeonggi-do, South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, Spain

Clínica Universidad de Navarra

Pamplona, Navarre, Spain

Hospital Clinic de Barcelona (Hospital Clinic i Provincial)

Barcelona, , Spain

Hospital Universitario Fundacion Jimenez Diaz.

Madrid, , Spain

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan, , Taiwan

Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital

Tainan, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

National Taiwan University Hospital (NTUH) - Cancer Research Center

Zhongzheng Dist., , Taiwan

Imperial College London - Imperial Centre for Translational and Experimental Medicine (ICTEM)

London, , United Kingdom

Countries

United States; Austria; France; Germany; New Zealand; South Korea; Spain; Taiwan; United Kingdom

Other Identifiers

GO44457

Identifier Type: -

Identifier Source: org_study_id