KN046 Combined With Ningatinib in the Treatment of Advanced Hepatocellular Carcinoma

Alphamab

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Advanced HCC

Treatments: Drug: KN046 （PD-L1/CTLA4 BsAb）; Drug: Ningetinib Tosylate（multi-target TKI）

Study type: Interventional

Funder types: Industry

Identifiers

NCT04601610

KN046-208

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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;

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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6 participants in 2 patient groups

Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Ningetinib Tosylate（multi-target TKI）

Drug: KN046 （PD-L1/CTLA4 BsAb）

Cohort 2

Experimental group

Description:

Subjects who have received at least first-line system treatment

Treatment:

Drug: Ningetinib Tosylate（multi-target TKI）

Drug: KN046 （PD-L1/CTLA4 BsAb）