The Study of KN046 in Combination With Lenvatinib in Advanced Hepatocellular Carcinoma
The Study of KN046 in Combination With Lenvatinib in Advanced Hepatocellular Carcinoma
This ia a single-arm, not-randomized, open-label phase II study. The purpose of this study is
 to evaluate the safety and efficacy of KN046 (PD-L1 /CTLA-4 Bispecific antibody) combined
 with Lenvatinib(TKI) for the treatment of advanced hepatocellular carcinoma.
Inclusion Criteria:

 -  Has a diagnosis of hepatocellular carcinoma confirmed by histology or cytology；

 -  Barcelona Clinic Liver Cancer (BCLC) Stage B or C；

 -  Age ≥18 years or ≤75 years for both genders；

 -  ECOG performance status: 0-1；

 -  Child Pugh score≤7；

 -  LVEF≥50% or above LLN of the research institution；

 -  Enough organ function；

 -  Has at least one measurable lesion based on RECIST 1.1；

 -  Life expectancy ≥3 months；

 -  Patients must be able to understand and willing to sign a written informed consent
 document；

 Exclusion Criteria:

 -  Fibrous lamina hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma,
 cholangiocarcinoma etc;

 -  Tumor thrombus invasion at the main portal vein (Vp4), inferior vena cava or heart
 involvement;

 -  Subjects who have previously received immune checkpoint inhibitors (such as
 anti-PD-1/L1, CTLA-4, etc.);

 -  Subjects who have received liver local treatment (transcatheter chemoembolization,
 transcatheter embolization, hepatic artery perfusion, radiotherapy, radioembolization
 or ablation) within 4 weeks before administration;

 -  Subjects who need corticosteroids or immunosuppressive agents for systemic therapy;

 -  Any previous or current active autoimmune disease or history of autoimmune disease;

 -  History of hepatic encephalopathy or liver transplantation;

 -  History of interstitial lung disease or non-infectious pneumonia;

 -  History of allergic reactions to related drugs;

 -  Clinically obvious gastrointestinal abnormalities, which may affect the intake,
 transport or absorption of drugs (such as inability to swallow, chronic diarrhea,
 intestinal obstruction, etc.), or patients undergoing total gastrectomy;

 -  With serious systemic diseases such as heart disease and cerebrovascular disease, and
 the condition is unstable or uncontrollable;

 -  Subjects with clinically significant gastrointestinal bleeding or thrombosis or
 embolic events within 6 months;

 -  Untreated hepatitis infection: HBV DNA>2000IU/ml or10000 copies/ml, HCV RNA>
 1000copy/ml, both HbsAg and anti-HCV body are positive;

 -  Evidence of active pulmonary tuberculosis (TB);

 -  Positive test of immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
 (AIDS);

 -  Pleural effusion, ascites and pericardial effusion with clinical symptoms or needing
 drainage;