KN046 Combined With Ningatinib in the Treatment of Advanced Hepatocellular Carcinoma

NCT ID: NCT04601610

Last Updated: 2022-10-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-07
• Study Completion Date: 2022-05-30

Brief Summary

This study is an open, multi-center clinical trial, the purpose is to study the safety and preliminary efficacy of KN046 combined with Ningatinib in subjects with advanced hepatocellular carcinoma.

Detailed Description

The study consists of dose escalation and dose expansion, the mTPI-2 (Modified Toxicity Probability Interval) will be used for dose exploration. The preset dose of KN046 is 5 mg/kg Q3W and the preset dose of ningatinib is 10 mg (rapid titration), 20 mg QD, 30 mg QD, and 40 mg QD.Dose expansion will be divided into two cohorts, cohort 1 will enroll subjects who have not received system therapy and cohort 2 will enroll subjects who have previously received at least first-line system therapy.

Conditions

Advanced HCC

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

Subjects who have not received first-line system treatment previously;

Group Type: EXPERIMENTAL

KN046 （PD-L1/CTLA4 BsAb）

Intervention Type: DRUG

KN046 5mg/kg Q3W

Ningetinib Tosylate（multi-target TKI）

Intervention Type: DRUG

ningtinib QD, dose will be decided by investigator

Cohort 2

Subjects who have received at least first-line system treatment

Group Type: EXPERIMENTAL

KN046 （PD-L1/CTLA4 BsAb）

Intervention Type: DRUG

KN046 5mg/kg Q3W

Ningetinib Tosylate（multi-target TKI）

Intervention Type: DRUG

ningtinib QD, dose will be decided by investigator

Interventions

KN046 （PD-L1/CTLA4 BsAb）

KN046 5mg/kg Q3W

Intervention Type: DRUG

Ningetinib Tosylate（multi-target TKI）

ningtinib QD, dose will be decided by investigator

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Has a diagnosis of hepatocellular carcinoma confirmed by histology or cytology；
• Barcelona Clinic Liver Cancer (BCLC) Stage B or C；
• ECOG performance status: 0-1；
• Child Pugh score≤7；
• 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;
• Past or present hepatic encephalopathy; or Budd-Chiari syndrome; or 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.); or have a history of ≥ grade 3 immune-related adverse reactions; or hyperprogressive after immunotherapy previously；
• 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 liver transplantation;
• History of interstitial lung disease or non-infectious pneumonia;
• History of allergic reactions to related drugs;
• LVEF< 50% or LLN
• 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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sunshine Lake Pharma Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Jiangsu Alphamab Biopharmaceuticals Co., Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

JianMing Xu, Doctor

Role: PRINCIPAL_INVESTIGATOR

301 Hospital of PLA，Beijing，China

ShanZhi Gu, Doctor

Role: PRINCIPAL_INVESTIGATOR

Hunan Cancer Hospital

YuXian Bai, Doctor

Role: PRINCIPAL_INVESTIGATOR

Harbin Medical University

Locations

Chinese Pla General Hospital Chinese Pla Medical School

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

KN046-208

Identifier Type: -

Identifier Source: org_study_id