A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)
NCT ID: NCT04524871
Last Updated: 2026-01-07
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
518 participants
INTERVENTIONAL
2020-11-01
2026-12-31
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Stage 1: Atezolizumab + Bevacizumab
Participants 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.
Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV on Day 1 of each 21 day cycle.
Bevacizumab 15 mg/kg
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.
Stage 1: Atezolizumab + Bevacizumab + Tiragolumab
Participants 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.
Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV on Day 1 of each 21 day cycle.
Bevacizumab 15 mg/kg
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.
Tiragolumab
Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.
Stage 1: Atezolizumab + Bevacizumab + Tocilizumab
Participants 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.
Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV on Day 1 of each 21 day cycle.
Bevacizumab 15 mg/kg
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.
Tocilizumab
Tocilizumab will be administered at a dose of 8 mg/kg by IV infusion on Day 1 of each 21 day cycle.
Stage 1: Atezolizumab + Bevacizumab + TPST-1120
Participants 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.
Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV on Day 1 of each 21 day cycle.
Bevacizumab 15 mg/kg
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.
TPST-1120
TPST-1120 will be administered at a dose of 1200 mg by mouth on Days 1-21 of each 21 day cycle.
Stage 1: Tobemstomig 2100 mg Q2W + Bevacizumab
Participants 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.
Bevacizumab 15 mg/kg
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.
Tobemstomig 2100 mg
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/kg
Bevacizumab will be administered at a dose of 10 mg/kg by IV infusion on Days 1 and 15 of each 28 day cycle.
Stage 1: Tobemstomig 600 mg Q3W + Bevacizumab
Participants 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.
Bevacizumab 15 mg/kg
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.
Tobemstomig 600 mg
Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.
Stage 1: Tobemstomig 1200 mg Q3W + Bevacizumab
Participants 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.
Bevacizumab 15 mg/kg
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.
Tobemstomig 1200 mg
Tobemstomig will be administered at a dose of 1200 mg every 3 weeks.
Stage 1: Atezolizumab + Bevacizumab + ADG126
Participants 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.
Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV on Day 1 of each 21 day cycle.
Bevacizumab 15 mg/kg
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.
ADG126
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).
Stage 1: Atezolizumab + Bevacizumab + IO-108 1200 mg Q3W
Participants 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.
Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV on Day 1 of each 21 day cycle.
Bevacizumab 15 mg/kg
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.
IO-108 1200 mg
IO-108 will be administered at a dose 1200 mg by IV infusion on Day 1 of each 21 day cycle.
Stage 1: Atezolizumab + Bevacizumab + NKT2152
Participants 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.
Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV on Day 1 of each 21 day cycle.
Bevacizumab 15 mg/kg
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.
NKT2152
NKT2152 will be administered by mouth.
Stage 1: Atezolizumab + Bevacizumab+ IO-108 1800 mg Q3W
Participants 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
IO-108 1800 mg
IO-108 will be administered at a dose 1800 mg by IV infusion on Day 1 of each 21 day cycle.
Interventions
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Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV on Day 1 of each 21 day cycle.
Bevacizumab 15 mg/kg
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.
Tiragolumab
Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.
Tocilizumab
Tocilizumab will be administered at a dose of 8 mg/kg by IV infusion on Day 1 of each 21 day cycle.
TPST-1120
TPST-1120 will be administered at a dose of 1200 mg by mouth on Days 1-21 of each 21 day cycle.
Tobemstomig 2100 mg
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/kg
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 mg
Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.
Tobemstomig 1200 mg
Tobemstomig will be administered at a dose of 1200 mg every 3 weeks.
ADG126
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 mg
IO-108 will be administered at a dose 1800 mg by IV infusion on Day 1 of each 21 day cycle.
NKT2152
NKT2152 will be administered by mouth.
IO-108 1200 mg
IO-108 will be administered at a dose 1200 mg by IV infusion on Day 1 of each 21 day cycle.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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)
Exclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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Adagene Inc
INDUSTRY
Tempest Therapeutics
INDUSTRY
NiKang Therapeutics, Inc.
INDUSTRY
Immune-Onc Therapeutics
INDUSTRY
Hoffmann-La Roche
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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UC Irvine Medical Center
Costa Mesa, California, United States
City of Hope
Duarte, California, United States
University of California San Diego
La Jolla, California, United States
UC Irvine Medical Center
Orange, California, United States
University of California San Francisco Cancer Center
San Francisco, California, United States
UCLA Center for East
Santa Monica, California, United States
Cherry Creek Medical Center
Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Cancer Pavilion
Aurora, Colorado, United States
UCHealth Cancer Center Pharmacy - Highlands Ranch Hospital
Highlands Ranch, Colorado, United States
Smilow Cancer Hospital at Yale New Haven
New Haven, Connecticut, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
University of Kentucky - Markey Cancer Center
Lexington, Kentucky, United States
Oregon Health & Science University
Portland, Oregon, United States
Sarah Cannon Research Institute / Tennessee Oncology
Nashville, Tennessee, United States
Parkland Health & Hospital System
Dallas, Texas, United States
The University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States
Beijing Cancer Hospital
Beijing, , China
Zhongshan Hospital Fudan University
Shanghai, , China
Centre Georges Francois Leclerc
Dijon, , France
CHU Hôpitaux de Marseille
Marseille, , France
Centre Eugène Marquis
Rennes, , France
Gustave Roussy
Villejuif, , France
Rambam Medical Center
Haifa, , Israel
Hadassah University Medical Center
Jerusalem, , Israel
Davidof Center - Rabin Medical Center
Petah Tikva, , Israel
Sourasky Medical Centre
Tel Aviv, , Israel
Auckland City Hospital
Auckland, , New Zealand
CHA Bundang Medical Center
Gyeonggi-do, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
Asan Medical Center
Seoul, , South Korea
National Cheng Kung University Hospital
Tainan, , Taiwan
National Taiwan University Hospital
Taipei, , Taiwan
Countries
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Central Contacts
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Reference Study ID Number: GO42216 https://forpatients.roche.com/
Role: CONTACT
References
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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.
Other Identifiers
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GO42216
Identifier Type: -
Identifier Source: org_study_id
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