RECRUITING

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

Conditions

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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)

Quick Facts

Study Start:2020-11-02

Study Completion:2026-08-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04524871

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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 * 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 * 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) * 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)	* 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 * 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

Inclusion Criteria

Exclusion Criteria

* 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
* 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
* 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)
* 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)

* 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
* 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

Contacts and Locations

Study Contact

Reference Study ID Number: GO42216 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. and Canada)

global.rochegenentechtrials@roche.com

Principal Investigator

Clinical Trials

STUDY_DIRECTOR

Hoffmann-La Roche

Study Locations (Sites)

UC Irvine Medical Center

Costa Mesa, California, 92627

United States

City of Hope

Duarte, California, 91010

United States

University of California San Diego

La Jolla, California, 92037-1337

United States

UC Irvine Medical Center

Orange, California, 92868

United States

University of California San Francisco Cancer Center; Pharmacy

San Francisco, California, 94115

United States

UCLA Center for East; West Medicine

Santa Monica, California, 90404

United States

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, 06510

United States

Georgetown University Medical Center

Washington, District of Columbia, 20007

United States

Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee, 37203

United States

The University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390

United States

Collaborators and Investigators

Sponsor: Hoffmann-La Roche

Clinical Trials, STUDY_DIRECTOR, Hoffmann-La Roche

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-11-02

Study Completion Date2026-08-31

Study Record Updates

Study Start Date2020-11-02

Study Completion Date2026-08-31

Terms related to this study

Additional Relevant MeSH Terms

Advanced Liver Cancers