Clinical trial NCT04601610: KN046 Combined With Ningatinib in the Treatment of Advanced Hepatocellular Carcinoma
Official title: An Open, Multi-center, Ib/II Clinical Trial of KN046 Combined With Ningatinib in the Treatment of Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced HCC
Lead sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Sunshine Lake Pharma Co., Ltd.
First posted: 2020-10-26
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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;

Primary outcomes:
measure: DLT
timeFrame: 1 months
measure: ORR
timeFrame: 1 years
Secondary outcomes:
measure: PFS
timeFrame: 1.5 years
measure: OS
timeFrame: 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese Pla General Hospital Chinese Pla Medical School
state: Beijing
Study officials:
affiliation: 301 Hospital of PLA，Beijing，China
name: JianMing Xu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Hunan Cancer Hospital
name: ShanZhi Gu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Harbin Medical University
name: YuXian Bai, Doctor
role: PRINCIPAL_INVESTIGATOR
References: