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

A Phase II Study Evaluating the Safety and Efficacy 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.

Study Overview

• Status: Completed
• Conditions: HCC
• Intervention / Treatment: Biological: KN046; Drug: Lenvatinib

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: KN046 plus Lenvatinib

Biological: KN046; 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.; Drug: Lenvatinib; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2020
• Primary Completion (Actual): February 23, 2022
• Study Completion (Actual): March 15, 2024

Study Registration Dates

• First Submitted: September 2, 2020
• First Submitted That Met QC Criteria: September 2, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: 20200825

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No