Actively Recruiting
A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)
Led by Hoffmann-La Roche · Updated on 2026-04-23
518
Participants Needed
33
Research Sites
360 weeks
Total Duration
On this page
Sponsors
H
Hoffmann-La Roche
Lead Sponsor
A
Adagene Inc
Collaborating Sponsor
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization
- Diagnosis of locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) confirmed by histology/cytology or clinically in cirrhotic patients
- Child-Pugh class A liver function within 7 days prior to randomization
- Disease not suitable for curative surgical or locoregional therapies
- No prior systemic treatment for HCC
- Life expectancy of at least 3 months
- Availability of a tumor specimen suitable for PD-L1 and other biomarker testing via central lab
- Measurable disease according to RECIST v1.1
- Adequate blood and organ function within 7 days prior to treatment start
- Documented hepatitis B and C virology status
- Negative HIV test at screening
- For women of childbearing potential: agreement to use contraception or remain abstinent
- For men: agreement to use contraception or remain abstinent and refrain from donating sperm
- ECOG Performance Status of 0, 1, or 2 for Stage 2
- Ability to start Stage 2 treatment within 3 months after loss of benefit or toxicity from Stage 1
- Availability of a tumor biopsy from discontinuation of Stage 1 treatment if feasible
- For NKT2152 arm: total bilirubin ≤ 1.5x upper limit of normal (ULN) without Gilbert's disease or ≤ 3.0x ULN with Gilbert's disease
- AST/ALT ≤ 2.5x ULN or ≤ 5x ULN if liver metastases present
You will not qualify if you...
- Prior treatment with CD137 agonists, immune checkpoint inhibitors, or HIF2a inhibitors
- Investigational therapy within 28 days before study start
- Locoregional liver therapy within 28 days before study or unresolved side effects
- Untreated or high-risk esophageal or gastric varices for bleeding
- Bleeding event from varices within 6 months before study
- Unresolved adverse events from prior cancer therapy except alopecia
- Uncontrolled hypertension or history of hypertensive crisis
- Significant vascular disease or recent hemoptysis
- Bleeding disorders or use of high-dose aspirin or certain antiplatelet/anticoagulant drugs
- Recent core biopsy or minor surgery within 3 days before study
- History of abdominal fistula, GI perforation, abscess, obstruction, or free air
- Non-healing wounds, active ulcers, or untreated fractures
- Proteinuria Grade ≥2
- Metastases affecting major airways or blood vessels
- Recent radiotherapy or major surgery within specified time frames
- Chronic daily NSAID use
- Eligible only for control arm
- Fibrolamellar or sarcomatoid HCC, mixed cholangiocarcinoma/HCC
- History of hepatic encephalopathy or moderate/severe ascites
- HBV and HCV coinfection
- Untreated or progressing central nervous system metastases
- History of leptomeningeal disease
- Uncontrolled pain, effusions, or hypercalcemia
- Active or history of autoimmune disease or immune deficiency
- History or evidence of pneumonitis or active tuberculosis
- Significant cardiovascular disease within 3 months or unstable heart conditions
- Recent major surgery other than diagnosis or anticipated major surgery during study
- History of other malignancies within 5 years
- Severe infection or antibiotic treatment shortly before study
- Prior allogeneic stem cell or organ transplantation
- Recent live attenuated vaccine or allergy to study drugs
- Recent immunostimulatory or immunosuppressive therapy
- Grade ≥3 bleeding within 8 weeks before study
- Unresolved immunotherapy-related adverse events for Stage 2 participants
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 33 locations
1
UC Irvine Medical Center
Costa Mesa, California, United States, 92627
Actively Recruiting
2
City of Hope
Duarte, California, United States, 91010
Actively Recruiting
3
UC Irvine Medical Center
Orange, California, United States, 92868
Actively Recruiting
4
University of California San Diego Medical Center
San Diego, California, United States, 92103
Actively Recruiting
5
University of California San Francisco Cancer Center
San Francisco, California, United States, 94115
Actively Recruiting
6
UCLA Center for East
Santa Monica, California, United States, 90404
Actively Recruiting
7
Cherry Creek Medical Center
Aurora, Colorado, United States, 80045
Actively Recruiting
8
University of Colorado Hospital - Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
Actively Recruiting
9
UCHealth Cancer Center Pharmacy - Highlands Ranch Hospital
Highlands Ranch, Colorado, United States, 80129-6694
Actively Recruiting
10
Smilow Cancer Hospital at Yale New Haven
New Haven, Connecticut, United States, 06510
Actively Recruiting
11
Georgetown University Medical Center
Washington D.C., District of Columbia, United States, 20007
Actively Recruiting
12
University of Kentucky - Markey Cancer Center
Lexington, Kentucky, United States, 40536-7001
Actively Recruiting
13
Oregon Health & Science University
Portland, Oregon, United States, 97239
Actively Recruiting
14
Sarah Cannon Research Institute / Tennessee Oncology
Nashville, Tennessee, United States, 37203
Completed
15
Parkland Health & Hospital System
Dallas, Texas, United States, 75235
Actively Recruiting
16
The University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390
Actively Recruiting
17
Beijing Cancer Hospital
Beijing, China, 100036
Actively Recruiting
18
Zhongshan Hospital Fudan University
Shanghai, China, 200032
Completed
19
Centre Georges Francois Leclerc
Dijon, France, 21079
Active, Not Recruiting
20
CHU Hôpitaux de Marseille
Marseille, France
Actively Recruiting
21
Centre Eugène Marquis
Rennes, France, 35042
Active, Not Recruiting
22
Gustave Roussy
Villejuif, France, 94800
Active, Not Recruiting
23
Rambam Medical Center
Haifa, Israel, 3109601
Actively Recruiting
24
Hadassah University Medical Center
Jerusalem, Israel
Actively Recruiting
25
Davidof Center - Rabin Medical Center
Petah Tikva, Israel, 4941492
Actively Recruiting
26
Sourasky Medical Centre
Tel Aviv, Israel, 64239
Actively Recruiting
27
Auckland City Hospital
Auckland, New Zealand, 1023
Actively Recruiting
28
CHA Bundang Medical Center
Gyeonggi-do, South Korea, 13496
Active, Not Recruiting
29
Seoul National University Hospital
Seoul, South Korea, 03080
Withdrawn
30
Samsung Medical Center
Seoul, South Korea, 06351
Actively Recruiting
31
Asan Medical Center
Seoul, South Korea, 5505
Actively Recruiting
32
National Cheng Kung University Hospital
Tainan, Taiwan, 70457
Actively Recruiting
33
National Taiwan University Hospital
Taipei, Taiwan, 10002
Actively Recruiting
Research Team
R
Reference Study ID Number: GO42216 https://forpatients.roche.com/
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
11
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