A PHASE II, OPEN-LABEL, MULTI-COHORT, MULTICENTER STUDY IN PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA AND CHILD-PUGH B7 AND B8 CIRRHOSIS (ML44719 KIRROS)

For participants with inoperable hepatocellular carcinoma (HCC). HCC is also known as liver cancer. In addition, you have a type of liver disease called cirrhosis. This study is testing two drugs called atezolizumab and bevacizumab. Atezolizumab will be given with or without bevacizumab.

The purpose of this study is to assess the effects, good or bad, of atezolizumab with bevacizumab, or atezolizumab alone, in participants with advanced, inoperable liver cancer (HCC) and liver disease (cirrhosis). 

Atezolizumab with bevacizumab has been approved by the Food and Drug Administration (FDA). This means that this combination can be given for the treatment of inoperable or advanced liver cancer (HCC) in patients who have not received prior systemic treatment. However, atezolizumab alone is not approved to treat liver cancer (HCC). The use of atezolizumab alone in this study is investigational. An investigational use is one that is not approved by the United States Food and Drug Administration (FDA).

For more information, please visit:  https://clinicaltrials.gov/study/NCT06096779

Inova Schar Cancer Institute
A division of Inova Fairfax Hospital
8081 Innovation Park Drive 
Fairfax, VA 22031

• Adults 18 years of age or older
• Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/cytology or clinically
• Disease that is not amenable to curative surgical and/or locoregional therapies
• Measurable disease (at least one untreated target lesion) according to RECIST v1.1
• Participants who received prior locoregional therapy (e.g., radiofrequency ablation, percutaneous ethanol, or acetic acid injection, cryoablation, high intensity focused ultrasound, transarterial chemoembolization, transarterial embolization) are eligible provided the target lesion(s) have not been previously treated with locoregional therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST v1.1
• Child-Pugh B7 or B8 cirrhosis at screening and within 7 days prior to study treatment
• Negative HIV test at screening, with the following exception: individuals with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a nadir CD4 count higher than 200/mL, and have an undetectable viral load
• Documented virology status of hepatitis, as confirmed by screening HBV and HCV serology tests
   
• Patients with active HBV must have the following:
  • HBV DNA less than 500 IU/mL obtained within 28 days prior to initiation of study treatment
  • Received anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment (per local standard of care) for the length of the study
• Patients with HCV must have the following:
  • Either with resolved infection (as evidenced by detectable antibody and undetectable HCV RNA) OR
    Chronic infection (as evidenced by detectable antibody and detectable HCV RNA) (acute HCV infection is not permitted)
  • Patients with a history of HCV infection but who are negative for HCV RNA by PCR will be considered non-infected with HCV. Ongoing treatment for chronic HCV infection is permitted at start of study treatment at the investigator's discretion. Direct-acting antiviral agents are permitted with the exception of protease inhibitor-based regimens (e.g., glecaprevir, grazoprevir, paritaprevir, simeprevir, and voxilaprevir) which are prohibited. Ongoing treatment with ribavirin and interferon are prohibited.
    Additional eligibility in protocol

• Pregnancy/breastfeeding
• Prior systemic treatment (including systemic investigational agents) for locally advanced or metastatic and/or unresectable HCC
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti−CTLA-4, anti−PD-1, anti−PD-L1, and anti-TIGIT therapeutic antibodies
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Current or recent treatment with clopidogrel, dipyridamole, ticlopidine, or cilostazol
• Current or recent use of full dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies
• History of leptomeningeal disease
• Known fibrolamellar HCC, sarcomatoid HCC, other rare HCC variant, or mixed cholangiocarcinoma and HCC
• History of hepatic encephalopathy requiring hospitalization or treatment escalation within 6 months prior to study treatment, or any continued symptoms of encephalopathy despite medical management
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• Additional ineligibility in protocol.