An Open, Multi-center, Ib/II Clinical Trial of KN046 Combined With Ningatinib in the Treatment of Advanced Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- ORR
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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；
排除标准
- •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;
研究组 & 干预措施
Cohort 1
Subjects who have not received first-line system treatment previously;
干预措施: KN046 （PD-L1/CTLA4 BsAb） (Drug)
Cohort 1
Subjects who have not received first-line system treatment previously;
干预措施: Ningetinib Tosylate（multi-target TKI） (Drug)
Cohort 2
Subjects who have received at least first-line system treatment
干预措施: KN046 （PD-L1/CTLA4 BsAb） (Drug)
Cohort 2
Subjects who have received at least first-line system treatment
干预措施: Ningetinib Tosylate（multi-target TKI） (Drug)
结局指标
主要结局
ORR
时间窗: 1 years
objective response rate (ORR) based on the RECIST 1.1 by investigator
DLT
时间窗: 1 months
Dose limit toxicity
次要结局
- PFS(1.5 years)
- OS(3 years)