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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

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

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver) (NCT04524871) is a Phase 1 / Phase 2 interventional studying Advanced Liver Cancers, sponsored by Hoffmann-La Roche. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Advanced Liver Cancers, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

A target enrollment of 518 participants makes this a sizable late-stage trial. Studies in this range typically have enough power to detect clinically meaningful differences from a comparator and to characterize less-common side effects.

Who May Be Eligible (Plain English)

Who May Qualify: 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 Stage 2 - You should be able to carry out daily activities with 0 level of ability (ECOG 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 Should NOT Join This Trial: Stage 1 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 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 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: 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 * 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

Treatments Being Tested

DRUG

Atezolizumab

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

DRUG

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.

DRUG

Tiragolumab

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

DRUG

Tocilizumab

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

DRUG

TPST-1120

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

DRUG

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.

DRUG

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.

DRUG

Tobemstomig 600 mg

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

DRUG

Tobemstomig 1200 mg

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

DRUG

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).

DRUG

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.

DRUG

NKT2152

NKT2152 will be administered by mouth.

DRUG

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.

Locations (20)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

UC Irvine Medical Center
Costa Mesa, California, United States
City of Hope
Duarte, California, United States
UC Irvine Medical Center
Orange, California, United States
University of California San Diego Medical Center
San Diego, 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

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04524871), the sponsor (Hoffmann-La Roche), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04524871 clinical trial studying?

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 the… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT04524871?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04524871?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04524871. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04524871. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.