KN046 Combined With Ningatinib in the Treatment of Advanced Hepatocellular Carcinoma

NCT04601610 | Terminated Phase 1 DMC

• 1 other identifier: KN046-208
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced HCC

Outcome Measures

Primary Outcomes (2)

• DLT

  Dose limit toxicity

  1 months

• ORR

  objective response rate (ORR) based on the RECIST 1.1 by investigator

  1 years

Secondary Outcomes (2)

• PFS

  1.5 years

• OS

  3 years

Study Arms (2)

Cohort 1

EXPERIMENTAL

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

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

Cohort 2

EXPERIMENTAL

Subjects who have received at least first-line system treatment

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

Interventions

KN046 （PD-L1/CTLA4 BsAb） DRUG

KN046 5mg/kg Q3W

Cohort 1; Cohort 2

Ningetinib Tosylate（multi-target TKI） DRUG

ningtinib QD, dose will be decided by investigator

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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；

You may not qualify if:

• 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);

Sponsors & Collaborators

• Jiangsu Alphamab Biopharmaceuticals Co., Ltd: lead
• Sunshine Lake Pharma Co., Ltd.: collaborator

Study Sites (1)

Chinese Pla General Hospital Chinese Pla Medical School

Beijing, Beijing Municipality, 100071, China

Location

Study Officials

• JianMing Xu, Doctor

  301 Hospital of PLA，Beijing，China

  PRINCIPAL INVESTIGATOR

• ShanZhi Gu, Doctor

  Hunan Cancer Hospital

  PRINCIPAL INVESTIGATOR

• YuXian Bai, Doctor

  Harbin Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2020
• First Posted: October 26, 2020
• Study Start: June 7, 2021
• Primary Completion: May 30, 2022
• Study Completion: May 30, 2022
• Last Updated: October 28, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)