The Study of KN046 in Combination With Lenvatinib in Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II Study Evaluating the Safety and Efficacy of KN046 in Combination With Lenvatinib in Advanced Hepatocellular Carcinoma

Conditions
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HCC

Intervention / Treatment
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* Biological: KN046
* Drug: Lenvatinib


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KN046 plus Lenvatinib<br> | Biological: KN046<br>* 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.<br>Drug: Lenvatinib<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | objective response rate (ORR) based on the RECIST 1.1 by investigator | 1 year after the last patient's enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | objective response rate (ORR) based on the mRECIST 1.1 and imRECIST respectively by investigator | 1 year after the last patient's enrollment | 
| DCR | disease control rate (DCR) based on the RECIST 1.1，mRECIST 1.1 and imRECIST respectively by investigator | 1 year after the last patient's enrollment | 
| DOR | duration of response (DOR) based on the RECIST 1.1，mRECIST 1.1 and imRECIST respectively by investigator | 1 year after the last patient's enrollment | 
| TTR | time to response (TTR) based on the RECIST 1.1，mRECIST 1.1 and imRECIST respectively by investigator | 1 year after the last patient's enrollment | 
| PFS |  | 1 year after the last patient's enrollment | 
| OS-12m rate | 12-month overall survival rate | 1 year after the last patient's enrollment | 
| OS | overall survival | 2 year after the last patient's enrollment |