Hepatocellular CarcinomaPhase 1/2NCT04444167
A Study of Anti-PD-1/CTLA-4 Bispecific AK104 Plus Lenvatinib in First-line Advanced Hepatocellular Carcinoma
A Phase 1/2 study testing AK104 and Lenvatinib in people with Hepatocellular Carcinoma, run by Akeso at 1 site in China.
Trial summary
An open-label multi-center phase Ib/II study to evaluate the efficacy and safety of anti-PD-1/CTLA-4 bispecific antibody AK104 plus lenvatinib as the first-line therapy for patients with advanced hepatocellular carcinoma. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- AK104 and Lenvatinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteChina
- Study dates
- 7 Jul 2020to 20 Nov 2023
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed written informed consent form voluntarily.
- Histologically or cytologically documented hepatocellular carcinoma.
- BCLC stage C, and non-resectable BCLC stage B .
- At least one measurable lesion according to RECIST criteria.
- ECOG of 0 or 1.
- Adequate organ function.
- Estimated life expectancy of ≥3 months.
- For women of childbearing potential: agreement to remain abstinent; For men: agreement to remain abstinent.
Who cannot join
- Histologically or cytologically documented fibrolamellar hepatocellular carcinoma, sarcoma-like hepatocellular carcinoma, cholangiocarcinoma, etc.
- History of hepatic encephalopathy or liver transplantation.
- Clinical significance of hydrothorax, ascites or pericardial effusion.
- Central nervous system metastases and/or carcinomatous meningitis.
- Any risk of bleeding; severe bleeding tendency or coagulation dysfunction, or under thrombolytic therapy.
- Occurred arteriovenous thromboembolic events within 6 months before the first administration.
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- Tumor volume > 50% liver volume; portal vein tumor thrombus or inferior vena cava tumor thrombus.
- Inadequately controlled arterial hypertension.
- Attack of symptomatic congestive heart failure (LVEF<50%); History of congenital long QT syndrome.
- Known presence or history of interstitial lung disease or required hormone treatment interstitial lung disease.
- Severe infections.
- Receipt of any anti-tumor treatment, chemotherapy, targeted therapy, immunotherapy,
- Enrollment of another clinical study within 4 weeks prior to the first administration of study drugs.
- Unable to receive an enhanced CT or MRI scan of the liver.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label Multi-Center Phase Ib/II Study of Anti-PD-1/CTLA-4 Bispecific Antibody AK104 in Combination With Lenvatinib As the First-Line Therapy for Patients With Advanced Hepatocellular Carcinoma
An open-label multi-center phase Ib/II study to evaluate the efficacy and safety of anti-PD-1/CTLA-4 bispecific antibody AK104 plus lenvatinib as the first-line therapy for patients with advanced hepatocellular carcinoma.
Read the detailed description
This is a multi-center, multi-cohort, open-label phase 1b/2 clinical study to evaluate the anti-tumor activity, safety, PK profile, immunogenicity and potential biomarkers of AK104 plus lenvatinib for the treatment of advanced hepatocellular carcinoma.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- AK104, Lenvatinib
- Keywords
- VEGF, Anti-PD-1, Tyrosine Kinase Inhibitor (TKI), Anti-CTLA-4
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AK104Biological
Subjects will receive AK104 and lenvatinib until disease progression or for a maximum of 24 months
LenvatinibDrug
Subjects will receive AK104 and lenvatinib until disease progression for a maximum of 24 months
| Study group | Role | What they receive |
|---|---|---|
| AK104 and Lenvatinib | Experimental | AK104 6 mg/kg IV every 2 weeks (Q2W) Lenvatinib 12mg weight≥60kg or 8mg weight<60kg,PO QD Receives: Biological: AK104; Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.
Measured: Up to 2 years
Secondary outcomes (6)
Disease control rate (DCR)
The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.
Measured: Up to 2 years
Duration of response (DoR)
Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first
Measured: Up to 2 years
Progression-free survival (PFS)
Progression-free survival is defined as the time from the start of treatment with AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first.
Measured: Up to 2 years
Number of participants with adverse events (AEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Measured: the time of informed consent signed through 90 days after the last dose of AK104 and
Observed concentrations of AK104
The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
Measured: From first dose of AK104 through 90 days after last dose of AK104
Number of subjects who develop detectable anti-drug antibodies (ADAs)
The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).
Measured: From first dose of AK104 through 90 days after last dose of AK104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2020
- Study start7 Jul 2020
- Primary completion20 Nov 2023
- Study completion20 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by AkesoThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akeso
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Akeso Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Li Bai, MD, Principal investigator, Chinese PLA General HospitalShunchang Jiao, MD, Principal investigator, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04444167
- Sponsor's protocol ID
- AK104-206
- Status last verified
- Apr 2024
- First submitted
- 21 Jun 2020
- Last updated
- 25 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Qiao Q, Han C, Ye S, Li J, Shao G, Bai Y, Xu A, Sun M, Wang W, Wu J, Huang M, Song L, Huang L, Liu T, Liu W, Wang ZM, Li B, Xia M, Bai L. The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial. Front Immunol. 2023 Oct 24;14:1238667. doi: 10.3389/fimmu.2023.1238667. eCollection 2023.
PubMed 37942328
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Multi-Center Phase Ib/II Study of Anti-PD-1/CTLA-4 Bispecific Antibody AK104 in Combination With Lenvatinib As the First-Line Therapy for Patients With Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT04444167
- Acronym / sponsor ID
- AK104-206
- Conditions
- Hepatocellular Carcinoma
- Keywords
- VEGF, Anti-PD-1, Tyrosine Kinase Inhibitor (TKI), Anti-CTLA-4
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- AkesoIndustry (pharma, biotech, devices)
- Collaborators
- Akeso Pharmaceuticals, Inc.
- Study start
- 7 Jul 2020 (actual)
- Primary completion
- 20 Nov 2023 (actual)
- Study completion
- 20 Nov 2023 (actual)
- First posted
- 23 Jun 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.
An open-label multi-center phase Ib/II study to evaluate the efficacy and safety of anti-PD-1/CTLA-4 bispecific antibody AK104 plus lenvatinib as the first-line therapy for patients with advanced hepatocellular carcinoma.
Detailed description
This is a multi-center, multi-cohort, open-label phase 1b/2 clinical study to evaluate the anti-tumor activity, safety, PK profile, immunogenicity and potential biomarkers of AK104 plus lenvatinib for the treatment of advanced hepatocellular carcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AK104 and Lenvatinib | Experimental | Biological: AK104, Drug: LenvatinibAK104 6 mg/kg IV every 2 weeks (Q2W) Lenvatinib 12mg weight≥60kg or 8mg weight<60kg,PO QD |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Signed written informed consent form voluntarily.
- Histologically or cytologically documented hepatocellular carcinoma.
- BCLC stage C, and non-resectable BCLC stage B .
- At least one measurable lesion according to RECIST criteria.
- ECOG of 0 or 1.
Key exclusion criteria (14 listed)
- Histologically or cytologically documented fibrolamellar hepatocellular carcinoma, sarcoma-like hepatocellular carcinoma, cholangiocarcinoma, etc.
- History of hepatic encephalopathy or liver transplantation.
- Clinical significance of hydrothorax, ascites or pericardial effusion.
- Central nervous system metastases and/or carcinomatous meningitis.
- Any risk of bleeding; severe bleeding tendency or coagulation dysfunction, or under thrombolytic 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 |
|---|---|---|
| AK104Subjects will receive AK104 and lenvatinib until disease progression or for a maximum of 24 months | Biological | AK104 and Lenvatinib |
| LenvatinibSubjects will receive AK104 and lenvatinib until disease progression for a maximum of 24 months | Drug | AK104 and Lenvatinib |
Primary outcome
Objective response rate (ORR)
Time frame: Up to 2 years
ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.
6 secondary outcomes
Disease control rate (DCR)
Time frame: Up to 2 years
Duration of response (DoR)
Time frame: Up to 2 years
Progression-free survival (PFS)
Time frame: Up to 2 years
Number of participants with adverse events (AEs)
Time frame: the time of informed consent signed through 90 days after the last dose of AK104 and
Observed concentrations of AK104
Time frame: From first dose of AK104 through 90 days after last dose of AK104
Number of subjects who develop detectable anti-drug antibodies (ADAs)
Time frame: From first dose of AK104 through 90 days after last dose of AK104
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2024.
- Derived from this study: PubMed 37942328Qiao Q, Han C, Ye S, Li J, Shao G, Bai Y, Xu A, Sun M, Wang W, Wu J, Huang M, Song L, Huang L, Liu T, Liu W, Wang ZM, Li B, Xia M, Bai L. The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial. Front Immunol. 2023 Oct 24;14:1238667. doi: 10.3389/fimmu.2023.1238667. eCollection 2023.
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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.
Li Bai, MD principal investigator
Chinese PLA General Hospital
Shunchang Jiao, MD principal investigator
Chinese PLA General Hospital
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 AK104 and Lenvatinib in people with Hepatocellular Carcinoma, run by Akeso 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 14 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: finished, as of the sponsor's last update on 25 Apr 2024. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Objective response rate (ORR) (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04444167, which also lists 1 linked publication.
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 25 Apr 2024.