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

Launched by HOFFMANN-LA ROCHE · Aug 21, 2020

Keywords

ClinConnect Summary

The Morpheus-Liver trial is investigating how well different combinations of immunotherapy treatments work and how safe they are for people with advanced liver cancers, specifically hepatocellular carcinoma (HCC). This study is open to patients who have not received any prior systemic treatments for their cancer and are facing locally advanced or metastatic disease. Participants will be randomly assigned to different treatment groups to see which combination is most effective. If a participant does not benefit from the initial treatment or experiences significant side effects, they may have the option to switch to a different treatment combination.

To be eligible for the trial, participants should have a good performance status (which means they are generally well enough to participate), a confirmed diagnosis of advanced HCC, and a life expectancy of at least three months. They will also need to provide a tumor sample for testing. Throughout the trial, participants can expect regular check-ins to monitor their health and response to treatment. It's important to note that this trial is still recruiting, and both men and women within a specific age range can apply. Overall, the goal of this study is to find better treatment options for patients dealing with advanced liver cancer.

Gender

ALL

Eligibility criteria

• 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)
• 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 Criteria:
• • 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