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

Recruiting now · Phase 1/Phase 2

Conditions studied: Advanced Liver Cancers

In brief

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.

Key facts

Study ID

NCT04524871

Run by

Hoffmann-La Roche

People needed

518

Starts

2020-11-01

Expected to finish

2027-09-30

Last updated by the study team

2026-07-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• 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)

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
• 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

Where it is running

• UC Irvine Medical Center — Costa Mesa, California, United States (enrolling)
• City of Hope — Duarte, California, United States (enrolling)
• Rambam Medical Center — Haifa, Israel (enrolling)
• Hadassah University Medical Center — Jerusalem, Israel (enrolling)
• Davidof Center - Rabin Medical Center — Petah Tikva, Israel (enrolling)
• Sourasky Medical Centre — Tel Aviv, Israel (enrolling)
• Auckland City Hospital — Auckland, New Zealand (enrolling)
• Samsung Medical Center — Seoul, South Korea (enrolling)
• Asan Medical Center — Seoul, South Korea (enrolling)
• National Cheng Kung University Hospital — Tainan, Taiwan (enrolling)
• National Taiwan University Hospital — Taipei, Taiwan (enrolling)
• University of California San Diego Medical Center — San Diego, California, United States (enrolling)
• University of California San Francisco Cancer Center — San Francisco, California, United States (enrolling)
• UCLA Center for East — Santa Monica, California, United States (enrolling)
• Cherry Creek Medical Center — Aurora, Colorado, United States (enrolling)
• University of Colorado Hospital - Anschutz Cancer Pavilion — Aurora, Colorado, United States (enrolling)
• UCHealth Cancer Center Pharmacy - Highlands Ranch Hospital — Highlands Ranch, Colorado, United States (enrolling)
• Smilow Cancer Hospital at Yale New Haven — New Haven, Connecticut, United States (enrolling)
• Georgetown University Medical Center — Washington D.C., District of Columbia, United States (enrolling)
• University of Kentucky - Markey Cancer Center — Lexington, Kentucky, United States (enrolling)
• Oregon Health & Science University — Portland, Oregon, United States (enrolling)
• Parkland Health & Hospital System — Dallas, Texas, United States (enrolling)
• The University of Texas Southwestern Medical Center at Dallas — Dallas, Texas, United States (enrolling)
• CHU Hôpitaux de Marseille — Marseille, France (enrolling)
• UC Irvine Medical Center — Orange, California, United States

Full record on ClinicalTrials.gov

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