Advanced HCCPhase 1/2NCT04601610
KN046 Combined With Ningatinib in the Treatment of Advanced Hepatocellular Carcinoma
A Phase 1/2 study testing KN046 （PD-L1/CTLA4 BsAb） and Ningetinib Tosylate（multi-target TKI） in people with Advanced HCC, run by Jiangsu Alphamab Biopharmaceuticals Co., Ltd at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Advanced HCC
- What is being tested?
- KN046 （PD-L1/CTLA4 BsAb） and Ningetinib Tosylate（multi-target TKI）
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteChina
- Study dates
- 7 Jun 2021to 30 May 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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；
Who cannot join
- 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;
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- 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 locations and contacts
1 site in 1 country.
China1 site
Chinese Pla General Hospital Chinese Pla Medical School
Beijing, Beijing Municipality, 100071
About this study
Official title: An Open, Multi-center, Ib/II Clinical Trial of KN046 Combined With Ningatinib in the Treatment of Advanced Hepatocellular Carcinoma
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.
Read the 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
- Being tested
- KN046 （PD-L1/CTLA4 BsAb）, Ningetinib Tosylate（multi-target TKI）
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KN046 （PD-L1/CTLA4 BsAb）Drug
KN046 5mg/kg Q3W
Ningetinib Tosylate（multi-target TKI）Drug
ningtinib QD, dose will be decided by investigator
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Subjects who have not received first-line system treatment previously; Receives: 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 Receives: Drug: KN046 （PD-L1/CTLA4 BsAb）; Drug: Ningetinib Tosylate（multi-target TKI） |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT
Dose limit toxicity
Measured: 1 months
ORR
objective response rate (ORR) based on the RECIST 1.1 by investigator
Measured: 1 years
Secondary outcomes (2)
PFS
progression free survival
Measured: 1.5 years
OS
overall survival
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2020
- Study start7 Jun 2021
- Primary completion30 May 2022
- Study completion30 May 2022
Why it stopped: The sponsor's development strategy adjustment resolution is terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced HCCStudies of the same condition, open and under way.
- More trials run by Jiangsu Alphamab Biopharmaceuticals Co., LtdThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jiangsu Alphamab Biopharmaceuticals Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sunshine Lake Pharma Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- JianMing Xu, Doctor, Principal investigator, 301 Hospital of PLA，Beijing，ChinaShanZhi Gu, Doctor, Principal investigator, Hunan Cancer HospitalYuXian Bai, Doctor, Principal investigator, Harbin Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04601610
- Sponsor's protocol ID
- KN046-208
- Status last verified
- May 2022
- First submitted
- 19 Oct 2020
- Last updated
- 28 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open, Multi-center, Ib/II Clinical Trial of KN046 Combined With Ningatinib in the Treatment of Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT04601610
- Acronym / sponsor ID
- KN046-208
- Conditions
- Advanced HCC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor's development strategy adjustment resolution is terminated
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Jiangsu Alphamab Biopharmaceuticals Co., LtdIndustry (pharma, biotech, devices)
- Collaborators
- Sunshine Lake Pharma Co., Ltd.
- Study start
- 7 Jun 2021 (actual)
- Primary completion
- 30 May 2022 (actual)
- Study completion
- 30 May 2022 (actual)
- First posted
- 26 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: KN046 （PD-L1/CTLA4 BsAb）, Drug: Ningetinib Tosylate（multi-target TKI）Subjects who have not received first-line system treatment previously; |
| Cohort 2 | Experimental | Drug: KN046 （PD-L1/CTLA4 BsAb）, Drug: Ningetinib Tosylate（multi-target TKI）Subjects who have received at least first-line system treatment |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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；
Key exclusion criteria (17 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KN046 （PD-L1/CTLA4 BsAb）KN046 5mg/kg Q3W | Drug | Cohort 1, Cohort 2 |
| Ningetinib Tosylate（multi-target TKI）ningtinib QD, dose will be decided by investigator | Drug | Cohort 1, Cohort 2 |
Primary outcome
DLT
Time frame: 1 months
Dose limit toxicity
ORR
Time frame: 1 years
objective response rate (ORR) based on the RECIST 1.1 by investigator
2 secondary outcomes
PFS
Time frame: 1.5 years
OS
Time frame: 3 years
Results and safety
The study was stopped early (reason given: The sponsor's development strategy adjustment resolution is terminated). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
JianMing Xu, Doctor principal investigator
301 Hospital of PLA，Beijing，China
ShanZhi Gu, Doctor principal investigator
Hunan Cancer Hospital
YuXian Bai, Doctor principal investigator
Harbin Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing KN046 （PD-L1/CTLA4 BsAb） and Ningetinib Tosylate（multi-target TKI） in people with Advanced HCC, run by Jiangsu Alphamab Biopharmaceuticals Co., Ltd at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The sponsor's development strategy adjustment resolution is terminated). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DLT (time frame: 1 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2022; AzTrials last refreshed its copy on 8 Nov 2026.