Status:
RECRUITING
A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)
Lead Sponsor:
Hoffmann-La Roche
Collaborating Sponsors:
Adagene Inc
Tempest Therapeutics
Conditions:
Advanced Liver Cancers
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief 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 trea...
Eligibility Criteria
Inclusion
- 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
- 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
Key Trial Info
Start Date :
November 1 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2026
Estimated Enrollment :
518 Patients enrolled
Trial Details
Trial ID
NCT04524871
Start Date
November 1 2020
End Date
December 31 2026
Last Update
January 7 2026
Active Locations (33)
Enter a location and click search to find clinical trials sorted by distance.
1
UC Irvine Medical Center
Costa Mesa, California, United States, 92627
2
City of Hope
Duarte, California, United States, 91010
3
University of California San Diego
La Jolla, California, United States, 92093
4
UC Irvine Medical Center
Orange, California, United States, 92868