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Advanced Liver CancersPhase 1/2MORPHEUS-LIVERNCT04524871

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)

A Phase 1/2 study testing Atezolizumab, Bevacizumab 15 mg/kg and Tiragolumab in people with Advanced Liver Cancers, run by Hoffmann-La Roche at 32 sites in 7 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced liver cancers. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Liver Cancers
What is being tested?
Atezolizumab, Bevacizumab 15 mg/kg and Tiragolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
518 participants
Where
32 sitesin 7 countries
Study dates
1 Nov 2020to 30 Sep 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Stage 1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization
  • Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of
  • Liver Diseases criteria in cirrhotic patients
  • Child-Pugh class A within 7 days prior to randomization
  • Disease that is not amenable to curative surgical and/or locoregional therapies
Show all 22Show fewer
  • No prior systemic treatment for HCC
  • Life expectancy >= 3 months
  • Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing
  • Stage 1 and Stage 2
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1
  • Adequate hematologic and end-organ function within 7 days prior to initiation of study treatment
  • Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus - (HBV) and hepatitis C virus (HCV)
  • Negative HIV test at screening
  • For women of childbearing potential: agreement to remain abstinent or use contraception and for men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm
  • Stage 2
  • ECOG Performance Status of 0, 1, or 2
  • Ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab or RO7247669 or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment
  • Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible)
  • NKT2152-Containing Arm:
  • Total bilirubin ≤ 1.5 X ULN in the absence of Gilbert's disease (≤ 3.0 X ULN if Gilbert's disease)
  • AST/ALT ≤ 2.5 X ULN (≤ 5 X ULN if liver metastases present)

Who cannot join

  • Stage 1
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies or inhibitors targeting HIF2a
  • Treatment with investigational therapy within 28 days prior to initiation of study
  • Treatment with locoregional therapy to liver within 28 days prior to initiation of study, or non-recovery from side effects of any such procedure
  • Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding
  • Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study
Show all 51Show fewer
  • AEs from prior anti-cancer therapy that have not resolved to Grade <= 1 or better, with the exception of alopecia of any grade
  • Inadequately controlled hypertension
  • History of hypertensive crisis or hypertensive encephalopathy
  • Significant vascular disease
  • History of hemoptysis within 1 month prior to initiation of study
  • Evidence of bleeding diathesis or significant coagulopathy
  • Current or recent use of aspirin (>325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol
  • Current or recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose
  • Core biopsy or other minor surgical procedure within 3 days prior to initiation of study
  • History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess, intestinal obstruction and/or clinical signs/symptoms of GI obstruction
  • Evidence of abdominal free air not explained by paracentesis or recent surgery
  • Serious, non-healing/dehiscing wound, active ulcer, or untreated bone fracture
  • Grade >=2 proteinuria
  • Metastatic disease involving major airways/blood vessels, or centrally located mediastinal tumor masses of large volume
  • History of clinically significant intra-abdominal inflammatory process
  • Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to initiation of study with the exception of palliative radiotherapy to bone lesions within 7 days prior to initiation of study
  • Major surgery, open biopsy, or significant traumatic injury within 28 days prior to initiation of study; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study; or anticipation of need for major surgery during study or non-recovery from side effects of any such procedure
  • Chronic daily treatment with NSAID
  • Eligible only for control arm
  • Stage 1 and 2
  • Fibrolamellar or sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
  • History of hepatic encephalopathy
  • Moderate or severe ascites
  • HBV and HCV coinfection
  • Symptomatic, untreated, or actively progressing CNS metastases
  • History of leptomeningeal disease
  • Uncontrolled tumor-related pain
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  • Uncontrolled or symptomatic hypercalcemia
  • Active or history of autoimmune disease or immune deficiency
  • History of IPF, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
  • Active TB
  • Significant CV disease within 3 months prior to initiation of study, unstable arrhythmia, or unstable angina
  • Major surgery, other than for diagnosis, within 4 weeks prior to initiation of study, or anticipated major surgery during study
  • History of malignancy other than HCC within 5 years prior to screening
  • Severe infection within 4 weeks prior to initiation of study
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study
  • Prior allogeneic stem cell or solid organ transplantation
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
  • History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
  • Known allergy or hypersensitivity to any of the study drugs or any of their excipients
  • Treatment with systemic immunostimulatory, immunosuppressive agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study
  • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study
  • Grade >= 3 hemorrhage or bleeding event within 8 weeks prior to initiation of study treatment
  • Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at time of consent

Trial locations and contacts

32 sites in 7 countries.

32 sites in 7 countries

United States16 sites

  • Cherry Creek Medical Center

    Aurora, Colorado, 80045

  • University of Colorado Hospital - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • UC Irvine Medical Center

    Costa Mesa, California, 92627

  • Parkland Health & Hospital System

    Dallas, Texas, 75235

  • The University of Texas Southwestern Medical Center at Dallas

    Dallas, Texas, 75390

  • City of Hope

    Duarte, California, 91010

  • UCHealth Cancer Center Pharmacy - Highlands Ranch Hospital

    Highlands Ranch, Colorado, 80129-6694

  • University of Kentucky - Markey Cancer Center

    Lexington, Kentucky, 40536-7001

  • Sarah Cannon Research Institute / Tennessee Oncology

    Nashville, Tennessee, 37203

  • Smilow Cancer Hospital at Yale New Haven

    New Haven, Connecticut, 06510

  • UC Irvine Medical Center

    Orange, California, 92868

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • University of California San Diego Medical Center

    San Diego, California, 92103

  • University of California San Francisco Cancer Center

    San Francisco, California, 94115

  • UCLA Center for East

    Santa Monica, California, 90404

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

France4 sites

  • Centre Georges Francois Leclerc

    Dijon, 21079

  • CHU Hôpitaux de Marseille

    Marseille

  • Centre Eugène Marquis

    Rennes, 35042

  • Gustave Roussy

    Villejuif, 94800

Other trials in France

Israel4 sites

  • Rambam Medical Center

    Haifa, 3109601

  • Hadassah University Medical Center

    Jerusalem

  • Davidof Center - Rabin Medical Center

    Petah Tikva, 4941492

  • Sourasky Medical Centre

    Tel Aviv, 64239

Other trials in Israel

South Korea3 sites

  • CHA Bundang Medical Center

    Gyeonggi-do, 13496

  • Samsung Medical Center

    Seoul, 06351

  • Asan Medical Center

    Seoul, 5505

Other trials in South Korea

China2 sites

  • Beijing Cancer Hospital

    Beijing, 100036

  • Zhongshan Hospital Fudan University

    Shanghai, 200032

Other trials in China

Taiwan2 sites

  • National Cheng Kung University Hospital

    Tainan, 70457

  • National Taiwan University Hospital

    Taipei, 10002

Other trials in Taiwan

New Zealand1 site

  • Auckland City Hospital

    Auckland, 1023

Other trials in New Zealand

About this study

Official title: A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)

This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced liver cancers. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, modify the participant population, or introduce additional cohorts of participants with other types of advanced primary liver cancer.

Cohort 1 will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy for their disease. Eligible participants will initially be randomly assigned to one of several treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.

Being tested
Atezolizumab, Bevacizumab 15 mg/kg, Tiragolumab, Tocilizumab, TPST-1120

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called Tecentriq

    Atezolizumab will be administered at a dose of 1200 mg by IV on Day 1 of each 21 day cycle.

  • Bevacizumab 15 mg/kgDrug

    Also called Avastin

    Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.

  • TiragolumabDrug

    Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.

  • TocilizumabDrug

    Also called Actemra

    Tocilizumab will be administered at a dose of 8 mg/kg by IV infusion on Day 1 of each 21 day cycle.

  • TPST-1120Drug

    TPST-1120 will be administered at a dose of 1200 mg by mouth on Days 1-21 of each 21 day cycle.

  • Tobemstomig 2100 mgDrug

    Tobemstomig will be administered at a dose of 2100 mg by IV infusion on Days 1 and 15 of each 28 day cycle.

  • Bevacizumab 10 mg/kgDrug

    Also called Avastin

    Bevacizumab will be administered at a dose of 10 mg/kg by IV infusion on Days 1 and 15 of each 28 day cycle.

  • Tobemstomig 600 mgDrug

    Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.

  • Tobemstomig 1200 mgDrug

    Tobemstomig will be administered at a dose of 1200 mg every 3 weeks.

  • ADG126Drug

    ADG126 will be administered at a dose of 6 mg/kg by IV infusion on Day 1 of every other cycle (cycle length = 21 days).

  • IO-108 1800 mgDrug

    IO-108 will be administered at a dose 1800 mg by IV infusion on Day 1 of each 21 day cycle.

  • NKT2152Drug

    NKT2152 will be administered by mouth.

  • IO-108 1200 mgDrug

    IO-108 will be administered at a dose 1200 mg by IV infusion on Day 1 of each 21 day cycle.

Study groups in NCT04524871
Study groupRoleWhat they receive
Stage 1: Atezolizumab + BevacizumabActive comparatorParticipants will receive atezolizumab plus bevacizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Receives: Drug: Atezolizumab; Drug: Bevacizumab 15 mg/kg
Stage 1: Atezolizumab + Bevacizumab + TiragolumabExperimentalParticipants will receive atezolizumab plus bevacizumab plus tiragolumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Receives: Drug: Atezolizumab; Drug: Bevacizumab 15 mg/kg; Drug: Tiragolumab
Stage 1: Atezolizumab + Bevacizumab + TocilizumabExperimentalParticipants will receive atezolizumab plus bevacizumab plus tocilizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Receives: Drug: Atezolizumab; Drug: Bevacizumab 15 mg/kg; Drug: Tocilizumab
Stage 1: Atezolizumab + Bevacizumab + TPST-1120ExperimentalParticipants will receive atezolizumab plus bevacizumab plus TPST-1120 until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Receives: Drug: Atezolizumab; Drug: Bevacizumab 15 mg/kg; Drug: TPST-1120
Stage 1: Tobemstomig 2100 mg Q2W + BevacizumabExperimentalParticipants will receive Tobemstomig plus bevacizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Receives: Drug: Bevacizumab 15 mg/kg; Drug: Tobemstomig 2100 mg; Drug: Bevacizumab 10 mg/kg
Stage 1: Tobemstomig 600 mg Q3W + BevacizumabExperimentalParticipants will receive Tobemstomig plus bevacizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Receives: Drug: Bevacizumab 15 mg/kg; Drug: Tobemstomig 600 mg
Stage 1: Tobemstomig 1200 mg Q3W + BevacizumabExperimentalParticipants will receive Tobemstomig plus bevacizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Receives: Drug: Bevacizumab 15 mg/kg; Drug: Tobemstomig 1200 mg
Stage 1: Atezolizumab + Bevacizumab + ADG126ExperimentalParticipants will receive atezolizumab plus bevacizumab plus ADG126 until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Receives: Drug: Atezolizumab; Drug: Bevacizumab 15 mg/kg; Drug: ADG126
Stage 1: Atezolizumab + Bevacizumab + IO-108 1200 mg Q3WExperimentalParticipants will receive atezolizumab plus bevacizumab plus IO-108 until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Receives: Drug: Atezolizumab; Drug: Bevacizumab 15 mg/kg; Drug: IO-108 1200 mg
Stage 1: Atezolizumab + Bevacizumab + NKT2152ExperimentalParticipants will receive atezolizumab plus bevacizumab plus NKT2152 until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Receives: Drug: Atezolizumab; Drug: Bevacizumab 15 mg/kg; Drug: NKT2152
Stage 1: Atezolizumab + Bevacizumab+ IO-108 1800 mg Q3WExperimentalParticipants will receive atezolizumab plus bevacizumab plus IO-108 until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic andbiochemical data, local biopsy results (if available), and clinical status
Receives: Drug: IO-108 1800 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    ORR, defined as the proportion of participants with a complete response or partial response on two consecutive occasions >=4 weeks apart during Stage 1, as determined by the investigator according to RECIST v1.1.

    Measured: From randomization until disease progression or loss of clinical benefit (up to approximately 7-9 years)

Secondary outcomes (7)

  1. Progression Free Survival (PFS)

    PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1.

    Measured: Randomization to first occurrence of disease progression or death from any cause in Stage 1 (up to approximately 7-9 years)

  2. Overall Survival (OS)

    OS after randomization, defined as the time from randomization to death from any cause.

    Measured: Randomization to death from any cause (up to approximately 7-9 years)

  3. OS at Specific Timepoints

    OS at a specific timepoint, such as Month 6

    Measured: Randomization to a specific timepoint, such as Month 6

  4. Duration of Response (DOR)

    DOR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1.

    Measured: First occurrence of a documented objective response to disease progression or death (up to approximately 7-9 years)

  5. Disease Control

    Disease control, defined as stable disease for >=12 weeks or a complete or partial response, as determined by the investigator according to RECIST v1.1.

    Measured: Randomization to end of study (approximately 7-9 years)

  6. Percentage of Participants With Adverse Events During Stage 1

    Measured: Baseline through the end of the study (approximately 7-9 years)

  7. Percentage of Participants With Adverse Events During Stage 2

    Measured: Baseline through the end of the study (approximately 7-9 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Aug 2020
  2. Study start1 Nov 2020
  3. Primary completion30 Jul 2027 (estimated)
  4. Study completion30 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
518 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04524871
Sponsor's protocol ID
GO42216
Acronym
MORPHEUS-LIVER
Status last verified
Sep 2026
First submitted
21 Aug 2020
Last updated
3 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • Finn RS, Ryoo BY, Hsu CH, Li D, Burgoyne AM, Cotter C, Badhrinarayanan S, Wang Y, Yin A, Edubilli TR, Mahrus S, Secrest MH, Shemesh CS, Yu N, Hack SP, Cha E, Gane E. Tiragolumab in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (MORPHEUS-Liver): a randomised, open-label, phase 1b-2, study. Lancet Oncol. 2025 Feb;26(2):214-226. doi: 10.1016/S1470-2045(24)00679-X. Epub 2025 Jan 21.

    PubMed 39855251

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Atezolizumab, Bevacizumab 15 mg/kg and Tiragolumab in people with Advanced Liver Cancers, run by Hoffmann-La Roche at 32 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 51 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in United States, France, Israel, South Korea, China and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: From randomization until disease progression or loss of clinical benefit (up to approximately 7-9 years)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04524871, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026.

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