HCC
Conditions
Brief summary
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.
Interventions
BIOLOGICALKN046
Subjects enrolled in the study will be intravenously administered KN046 5mg/kg every 3 weeks (Q3W), until disease progression, or unacceptable toxicity, or withdrawal of consent, or lost to follow-up, or died, or treatment for 2 years, or the investigator decides to terminate.
DRUGLenvatinib
Subjects enrolled in the study will receive lenvatinib 12 mg (BW≥60 kg) or 8 mg (BW\<60 kg) orally once a day (QD) ,until disease progression, or unacceptable toxicity, or withdrawal of consent, or lost to follow-up, or died, or treatment for 2 years, or the investigator decides to terminate.
Sponsors
Peking University Cancer Hospital & Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 1 year after the last patient's enrollment | objective response rate (ORR) based on the RECIST 1.1 by investigator |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 1 year after the last patient's enrollment | objective response rate (ORR) based on the mRECIST 1.1 and imRECIST respectively by investigator |
| DCR | 1 year after the last patient's enrollment | disease control rate (DCR) based on the RECIST 1.1，mRECIST 1.1 and imRECIST respectively by investigator |
| DOR | 1 year after the last patient's enrollment | duration of response (DOR) based on the RECIST 1.1，mRECIST 1.1 and imRECIST respectively by investigator |
| TTR | 1 year after the last patient's enrollment | time to response (TTR) based on the RECIST 1.1，mRECIST 1.1 and imRECIST respectively by investigator |
| PFS | 1 year after the last patient's enrollment | — |
| OS-12m rate | 1 year after the last patient's enrollment | 12-month overall survival rate |
| OS | 2 year after the last patient's enrollment | overall survival |
Countries
China
Outcome results
None listed