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

  • STATUS
    Recruiting
  • End date
    Dec 22, 2024
  • participants needed
    320
  • sponsor
    Hoffmann-La Roche
Updated on 27 June 2022

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.

Details
Condition Advanced Liver Cancers
Treatment bevacizumab, Tocilizumab, Atezolizumab, SAR439459, Tiragolumab, RO7247669, TPST-1120, RO7247669 2100 mg, RO7247669 600 mg, RO7247669 1200 mg dose
Clinical Study IdentifierNCT04524871
SponsorHoffmann-La Roche
Last Modified on27 June 2022

Eligibility

Yes No Not Sure

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)

Exclusion Criteria

Stage 1
Prior treatment with CD137 agonists or immune checkpoint inhibitors
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 asprin (>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 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
Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at time of consent
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