A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)
MORPHEUS-LIVER
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)
1 other identifier
interventional
518
7 countries
33
Brief 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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2020
Longer than P75 for phase_1
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 21, 2020
CompletedFirst Posted
Study publicly available on registry
August 24, 2020
CompletedStudy Start
First participant enrolled
November 1, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 30, 2027
April 23, 2026
April 1, 2026
6.7 years
August 21, 2020
April 22, 2026
Conditions
Outcome Measures
Primary Outcomes (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.
From randomization until disease progression or loss of clinical benefit (up to approximately 7-9 years)
Secondary Outcomes (7)
Progression Free Survival (PFS)
Randomization to first occurrence of disease progression or death from any cause in Stage 1 (up to approximately 7-9 years)
Overall Survival (OS)
Randomization to death from any cause (up to approximately 7-9 years)
OS at Specific Timepoints
Randomization to a specific timepoint, such as Month 6
Duration of Response (DOR)
First occurrence of a documented objective response to disease progression or death (up to approximately 7-9 years)
Disease Control
Randomization to end of study (approximately 7-9 years)
- +2 more secondary outcomes
Study Arms (11)
Stage 1: Atezolizumab + Bevacizumab
ACTIVE 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.
Stage 1: Atezolizumab + Bevacizumab + Tiragolumab
EXPERIMENTALParticipants 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.
Stage 1: Atezolizumab + Bevacizumab + Tocilizumab
EXPERIMENTALParticipants 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.
Stage 1: Atezolizumab + Bevacizumab + TPST-1120
EXPERIMENTALParticipants 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.
Stage 1: Tobemstomig 2100 mg Q2W + Bevacizumab
EXPERIMENTALParticipants 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.
Stage 1: Tobemstomig 600 mg Q3W + Bevacizumab
EXPERIMENTALParticipants 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.
Stage 1: Tobemstomig 1200 mg Q3W + Bevacizumab
EXPERIMENTALParticipants 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.
Stage 1: Atezolizumab + Bevacizumab + ADG126
EXPERIMENTALParticipants 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.
Stage 1: Atezolizumab + Bevacizumab + IO-108 1200 mg Q3W
EXPERIMENTALParticipants 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.
Stage 1: Atezolizumab + Bevacizumab + NKT2152
EXPERIMENTALParticipants 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.
Stage 1: Atezolizumab + Bevacizumab+ IO-108 1800 mg Q3W
EXPERIMENTALParticipants 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
Interventions
Atezolizumab will be administered at a dose of 1200 mg by IV on Day 1 of each 21 day cycle.
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.
Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.
Tocilizumab will be administered at a dose of 8 mg/kg by IV infusion on Day 1 of each 21 day cycle.
TPST-1120 will be administered at a dose of 1200 mg by mouth on Days 1-21 of each 21 day cycle.
Tobemstomig will be administered at a dose of 2100 mg by IV infusion on Days 1 and 15 of each 28 day cycle.
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 will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.
Tobemstomig will be administered at a dose of 1200 mg every 3 weeks.
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 will be administered at a dose 1800 mg by IV infusion on Day 1 of each 21 day cycle.
IO-108 will be administered at a dose 1200 mg by IV infusion on Day 1 of each 21 day cycle.
Eligibility Criteria
You may qualify if:
- 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
- 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
- +7 more criteria
You may not qualify if:
- 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
- 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
- +36 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Hoffmann-La Rochelead
- Adagene Inccollaborator
- Tempest Therapeuticscollaborator
- NiKang Therapeutics, Inc.collaborator
- Immune-Onc Therapeuticscollaborator
Study Sites (33)
UC Irvine Medical Center
Costa Mesa, California, 92627, United States
City of Hope
Duarte, California, 91010, United States
UC Irvine Medical Center
Orange, California, 92868, United States
University of California San Diego Medical Center
San Diego, California, 92103, United States
University of California San Francisco Cancer Center
San Francisco, California, 94115, United States
UCLA Center for East
Santa Monica, California, 90404, United States
Cherry Creek Medical Center
Aurora, Colorado, 80045, United States
University of Colorado Hospital - Anschutz Cancer Pavilion
Aurora, Colorado, 80045, United States
UCHealth Cancer Center Pharmacy - Highlands Ranch Hospital
Highlands Ranch, Colorado, 80129-6694, United States
Smilow Cancer Hospital at Yale New Haven
New Haven, Connecticut, 06510, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007, United States
University of Kentucky - Markey Cancer Center
Lexington, Kentucky, 40536-7001, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
Sarah Cannon Research Institute / Tennessee Oncology
Nashville, Tennessee, 37203, United States
Parkland Health & Hospital System
Dallas, Texas, 75235, United States
The University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390, United States
Beijing Cancer Hospital
Beijing, 100036, China
Zhongshan Hospital Fudan University
Shanghai, 200032, China
Centre Georges Francois Leclerc
Dijon, 21079, France
CHU Hôpitaux de Marseille
Marseille, France
Centre Eugène Marquis
Rennes, 35042, France
Gustave Roussy
Villejuif, 94800, France
Rambam Medical Center
Haifa, 3109601, Israel
Hadassah University Medical Center
Jerusalem, Israel
Davidof Center - Rabin Medical Center
Petah Tikva, 4941492, Israel
Sourasky Medical Centre
Tel Aviv, 64239, Israel
Auckland City Hospital
Auckland, 1023, New Zealand
CHA Bundang Medical Center
Gyeonggi-do, 13496, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Asan Medical Center
Seoul, 5505, South Korea
National Cheng Kung University Hospital
Tainan, 70457, Taiwan
National Taiwan University Hospital
Taipei, 10002, Taiwan
Related Publications (1)
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.
PMID: 39855251DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Central Study Contacts
Reference Study ID Number: GO42216 https://forpatients.roche.com/
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 21, 2020
First Posted
August 24, 2020
Study Start
November 1, 2020
Primary Completion (Estimated)
July 30, 2027
Study Completion (Estimated)
September 30, 2027
Last Updated
April 23, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
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