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

December 5, 2025 updated by: Hoffmann-La Roche

A Phase Ib/II, Open-Label, Multicenter, Randomized Platform Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma (MORPHEUS-NEO HCC)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
62

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Austria
      • Klagenfurt, Austria, 9020
        • Klinikum Klagenfurt Am Worthersee
      • Vienna, Austria, 1100
        • Wiener Gesundheitsverbund, Klinik Favoriten
      • Vienna, Austria, 1180
        • Department of Internal Medicine III AKH and Medical University of Vienna
  • France
      • Dijon, France, 21079
        • Centre Georges François Leclerc (CGFL)
      • Rennes, France, 35042
        • Centre Eugene Marquis (CEM)
      • Villejuif, France, 94800
        • Gustave Roussy
      • Villejuif, France, 94800
        • Assistance Publique-Hôpitaux de Paris
  • Germany
      • Essen, Germany, 45147
        • University Essen
      • Frankfurt, Germany, 60596
        • Universitaets Klinikum Frankfurt - Zentrum der Inneren Medizin
      • Mainz, Germany, 55131
        • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
  • New Zealand
      • Auckland, New Zealand, 1023
        • Auckland District Health Board (ADHB)
  • South Korea
      • Seoul, South Korea, 05505
        • Asan Medical Center
      • Seoul, South Korea, 003-722
        • Severance Hospital, Yonsei University Health System
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, South Korea, 463-712
        • CHA Bundang Medical Center
  • Spain
      • Barcelona, Spain, 8036
        • Hospital Clinic de Barcelona (Hospital Clinic i Provincial)
      • Madrid, Spain, 28040
        • Hospital Universitario Fundacion Jimenez Diaz.
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Hospital Universitario Marqués de Valdecilla
    • Navarre
      • Pamplona, Navarre, Spain, 31620
        • Clínica Universidad de Navarra
  • Taiwan
      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital
      • Tainan, Taiwan, 70457
        • National Cheng Kung University Hospital
      • Tainan, Taiwan, 83301
        • Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital
      • Taipei, Taiwan, 112
        • Taipei Veterans General Hospital
      • Zhongzheng Dist., Taiwan, 10051
        • National Taiwan University Hospital (NTUH) - Cancer Research Center
  • United Kingdom
      • London, United Kingdom
        • Imperial College London - Imperial Centre for Translational and Experimental Medicine (ICTEM)
  • United States
    • California
      • Los Angeles, California, United States, 90033
        • University of Southern California (USC)
      • Santa Monica, California, United States, 90404-2023
        • University of California Los Angeles (UCLA) - Cancer Care - Santa Monica
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Georgetown University Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48201-2013
        • Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center - Main Campus
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • Texas
      • Dallas, Texas, United States, 75390-8813
        • UT Southwestern 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

General 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

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.
Other Names:
  • Tecentriq
Drug: Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
Other Names:
  • Avastin
Experimental: 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.
Drug: Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.
Other Names:
  • Tecentriq
Drug: Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
Other Names:
  • Avastin
Drug: Tiragolumab
Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1.
Experimental: 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.
Drug: Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
Other Names:
  • Avastin
Drug: Tobemstomig
Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1
Other Names:
  • RO7247669

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Major Pathologic Response (MPR) Rate
Time Frame: At the time of surgery
MPR rate is defined as the proportion of participants with =<10% residual viable tumor in the tumor bed at the time of surgery, as assessed by central pathological review.
At the time of surgery

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Relapse-Free Survival (RFS)
Time Frame: Surgery to the first documented recurrence of disease (up to approximately 2 years)
RFS is defined as the time from surgery to the first documented recurrence of disease (intrahepatic or extrahepatic) according to EASL and/or RECIST v1.1, or death from any cause.
Surgery to the first documented recurrence of disease (up to approximately 2 years)
Overall Survival (OS)
Time Frame: Randomization to death from any cause (up to approximately 3 years)
OS is defined as the time from randomization to death from any cause.
Randomization to death from any cause (up to approximately 3 years)
Proportion of Participants Downstaged to Within Milan Criteria
Time Frame: Prior to surgery
Proportion of participants downstaged to within Milan criteria (for participants beyond criteria at randomization). Within Milan criteria is defined as single tumor <= 5 cm or 2 - 3 nodules all <= 3 cm.
Prior to surgery
R0 Resection Rate
Time Frame: At the time of surgery
R0 resection rate (proportion of resected participants obtaining an R0 resection). R0 resection is defined as a microscopically margin-negative resection, in which no tumor (gross or microscopic) remains in the primary tumor bed.
At the time of surgery
Percentage of Participants With Adverse Events
Time Frame: Up to approximately 3 years after first participant enrolled
Up to approximately 3 years after first participant enrolled
Proportion of Participants With Delayed or Canceled Surgery Due to Treatment-Related Adverse Events
Time Frame: >28 days from surgical restaging visit, anticipated up to 56 days
Proportion of participants with delayed or canceled surgery due to treatment-related adverse events (defined as > 28 days from surgical restaging visit).
>28 days from surgical restaging visit, anticipated up to 56 days
Post-Operative Surgical Complication Rates According to The Clavien-Dindo Surgical Classification
Time Frame: Surgery to treatment completion/discontinuation (up to approximately 2 years)
Post-operative surgical complication rates according to the Clavien-Dindo surgical classification. Clinically relevant complications are defined as Clavien-Dindo Grade >= IIIa.
Surgery to treatment completion/discontinuation (up to approximately 2 years)
Pathologic Complete Response (pCR) Rate
Time Frame: At the time of surgery
pCR rate is defined as the proportion of participants with an absence of residual tumor at the time of surgery, as assessed by central pathological review.
At the time of surgery
Event-Free Survival (EFS)
Time Frame: Randomization up to approximately 3 years
EFS is defined as the time from randomization to any of the following events (whichever occurs first): disease progression that precludes surgery, as assessed by the investigator according RECIST v1.1; local regional, or distant disease recurrence as measured by EASL and/or RECIST v1.1; or death from any cause.
Randomization up to approximately 3 years
OS Rate at 24 Months
Time Frame: Randomization up to 24 months
OS rate at 24 months is defined as the proportion of participants who have not experience death from any cause at 24 months after randomization.
Randomization up to 24 months
OS Rate at 36 Months
Time Frame: Randomization up to 36 months
OS rate at 36 months is defined as the proportion of participants who have not experience death from any cause at 36 months after randomization.
Randomization up to 36 months
Objective Response Rate (ORR)
Time Frame: Prior to surgery
ORR is defined as the proportion of participants with a radiographic Complete Response (CR) or Partial Response (PR) prior to surgery, as determined by the investigator according to RECIST v1.1 and HCC mRECIST. Responses will be assessed and determined according to RECIST v1.1 and HCC mRECIST but are not required to be confirmed by subsequent imaging assessments.
Prior to surgery
Post-Operative Mortality
Time Frame: Within 90 days after surgery
Post-operative mortality is defined as death within 90 days after surgery
Within 90 days after surgery

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 5, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 27, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 13, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 7, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 15, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 18, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 11, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 5, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GO44457

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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