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)
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.
Arms & interventions
- DrugAtezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV on Day 1 of each 21 day cycle.
- DrugBevacizumab 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.
- DrugTiragolumab
Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.
- DrugTocilizumab
Tocilizumab will be administered at a dose of 8 mg/kg by IV infusion on Day 1 of each 21 day cycle.
- DrugTPST-1120
TPST-1120 will be administered at a dose of 1200 mg by mouth on Days 1-21 of each 21 day cycle.
- DrugTobemstomig 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.
- DrugBevacizumab 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.
- DrugTobemstomig 600 mg
Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.
- DrugTobemstomig 1200 mg
Tobemstomig will be administered at a dose of 1200 mg every 3 weeks.
- DrugADG126
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).
- DrugIO-108 1800 mg
IO-108 will be administered at a dose 1800 mg by IV infusion on Day 1 of each 21 day cycle.
- DrugNKT2152
NKT2152 will be administered by mouth.
- DrugIO-108 1200 mg
IO-108 will be administered at a dose 1200 mg by IV infusion on Day 1 of each 21 day cycle.
Outcome measures
Primary
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.
Time frame: From randomization until disease progression or loss of clinical benefit (up to approximately 7-9 years)
Secondary
Progression Free Survival (PFS)
Time frame: Randomization to first occurrence of disease progression or death from any cause in Stage 1 (up to approximately 7-9 years)
Overall Survival (OS)
Time frame: Randomization to death from any cause (up to approximately 7-9 years)
OS at Specific Timepoints
Time frame: Randomization to a specific timepoint, such as Month 6
Duration of Response (DOR)
Time frame: First occurrence of a documented objective response to disease progression or death (up to approximately 7-9 years)
Disease Control
Time frame: Randomization to end of study (approximately 7-9 years)
Percentage of Participants With Adverse Events During Stage 1
Time frame: Baseline through the end of the study (approximately 7-9 years)
Percentage of Participants With Adverse Events During Stage 2
Time frame: Baseline through the end of the study (approximately 7-9 years)
Eligibility criteria
Study locations (16)
UC Irvine Medical Center
Costa Mesa, California, 92627
City of Hope
Duarte, California, 91010
UC Irvine Medical Center
Orange, California, 92868
University of California San Diego Medical Center
San Diego, California, 92103
University of California San Francisco Cancer Center
San Francisco, California, 94115
UCLA Center for East
Santa Monica, California, 90404
Cherry Creek Medical Center
Aurora, Colorado, 80045
University of Colorado Hospital - Anschutz Cancer Pavilion
Aurora, Colorado, 80045
UCHealth Cancer Center Pharmacy - Highlands Ranch Hospital
Highlands Ranch, Colorado, 80129-6694
Smilow Cancer Hospital at Yale New Haven
New Haven, Connecticut, 06510
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
University of Kentucky - Markey Cancer Center
Lexington, Kentucky, 40536-7001
Oregon Health & Science University
Portland, Oregon, 97239
Sarah Cannon Research Institute / Tennessee Oncology
Nashville, Tennessee, 37203
Parkland Health & Hospital System
Dallas, Texas, 75235
The University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390
References
- 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.(PubMed)