HCCPhase 2NCT06984718
A Phase II Study of AK104 Combination With Lenvatinib Versus Lenvatinib for Second-line HCC
A Phase 2 study testing AK104+lenvatinib and lenvatinib in people with HCC and Hepatocellular Carcinoma, run by Akeso.
Trial summary
This is a Phase II, randomized, open-label, global, multi-center study to compare the efficacy and safety of AK104 in combination with lenvatinib versus lenvatinib in patients with advanced hepatocellular carcinoma who have progressed on the first line treatment of atezolizumab and bevacizumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HCC, Hepatocellular Carcinoma
- What is being tested?
- AK104+lenvatinib and lenvatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- No sites listed yet
- Study dates
- 25 Jun 2025to 30 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed the Informed Consent Form (ICF) voluntarily.
- Age ≥18 years at time of signing ICF.
- Histologic or cytologic confirmation of HCC, or clinical diagnosis of HCC as per AASLD criteria.
- BCLC stage B or C, and not suitable for curative surgical or local therapy.
- Participants have progressed on the prior first-line systemic treatment with atezolizumab plus bevacizumab combination treatment.
- At least one measurable lesion according to RECIST v1.1.
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- Child-Pugh Class A .
- ECOG performance status of 0 or 1.
- With a life expectancy of ≥3 months.
- Adequate organ and hematologic function.
Who cannot join
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- Tumor thrombus invasion of superior mesenteric vein.
- Has a known history of, or any evidence of CNS metastases.
- Has received anti-cancer therapy for HCC within 3 weeks prior to the first dose of study treatment.
- Has received systemic anti-cancer therapy other than atezolizumab and bevacizumab.
- Has participated in another clinical study within 4 weeks prior to the first dose.
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- History of liver transplantation.
- History of hepatic encephalopathy.
- Clinically symptomatic or recurrently drained pleural effusion, pericardial effusion, or ascites.
- History of bleeding event due to esophageal and/or gastric varices within 6 months prior to the first dose of study treatment.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Phase II, Randomized, Open-label, Multi-center Study of AK104 in Combination With Lenvatinib Versus Lenvatinib in Patients With Advanced Hepatocellular Carcinoma Who Have Progressed on Atezolizumab and Bevacizumab
This is a Phase II, randomized, open-label, global, multi-center study to compare the efficacy and safety of AK104 in combination with lenvatinib versus lenvatinib in patients with advanced hepatocellular carcinoma who have progressed on the first line treatment of atezolizumab and bevacizumab.
- Conditions
- HCC, Hepatocellular Carcinoma
- Being tested
- AK104+lenvatinib, lenvatinib
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AK104+lenvatinibBiological
Subjects will receive AK104+lenvatinib until disease progression
lenvatinibDrug
Subjects will receive lenvatinib until disease progression
| Study group | Role | What they receive |
|---|---|---|
| AK104+lenvatinib | Experimental | AK104 IV plus lenvatinib orally Receives: Biological: AK104+lenvatinib |
| lenvatinib | Active comparator | lenvatinib orally Receives: Drug: lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) per RECIST v1.1 by Blinded Independent Central Review (BICR)
Proportion of subjects who have a complete or partial response relative to baseline as assessed by BICR according to RECIST v1.1.
Measured: Up to 24 months
Secondary outcomes (5)
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause.
Measured: Up to 24 months
Progression-free survival (PFS) assessed by investigator per RECIST v1.1
PFS is defined as the time from randomization till the first documented disease progression (Per RECIST v1.1 assessed by the investigator) or death due to any cause, whichever occurs first.
Measured: Up to 24 months
Duration of Response (DOR) assessed by investigator per RECIST v1.1
DOR means time measured from the date of partial or complete response to therapy until the cancer progresses based on RECIST v1.1 criteria.
Measured: Up to 24 months
Time to Response (TTR) assessed by investigator per RECIST v1.1
TTR refers to Time to Response.
Measured: Up to 24 months
Number of participants with adverse event (AE)
The number of participants experiencing an Adverse Event (AE) and the severity of AEs will be assessed. AE refers to any untoward medical occurrence or deterioration of existing medical event after the subject signed the ICF, whether or not considered related to the study treatment.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2025
- Study start25 Jun 2025 (estimated)
- Primary completion30 Nov 2026 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HCCStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Akeso
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Richard S. Finn, Ph.D., Principal investigator, Department of Medicine, University of CaliforniaJian Zhou, Ph.D., Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06984718
- Sponsor's protocol ID
- AK104-225
- Status last verified
- May 2025
- First submitted
- 15 May 2025
- Last updated
- 22 May 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Open-label, Multi-center Study of AK104 in Combination With Lenvatinib Versus Lenvatinib in Patients With Advanced Hepatocellular Carcinoma Who Have Progressed on Atezolizumab and Bevacizumab
- ClinicalTrials.gov ID
- NCT06984718
- Acronym / sponsor ID
- AK104-225
- Conditions
- HCC, Hepatocellular Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- AkesoIndustry (pharma, biotech, devices)
- Study start
- 25 Jun 2025 (estimated)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 22 May 2025 (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 is a Phase II, randomized, open-label, global, multi-center study to compare the efficacy and safety of AK104 in combination with lenvatinib versus lenvatinib in patients with advanced hepatocellular carcinoma who have progressed on the first line treatment of atezolizumab and bevacizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AK104+lenvatinib | Experimental | Biological: AK104+lenvatinibAK104 IV plus lenvatinib orally |
| lenvatinib | Active comparator | Drug: lenvatiniblenvatinib orally |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Signed the Informed Consent Form (ICF) voluntarily.
- Age ≥18 years at time of signing ICF.
- Histologic or cytologic confirmation of HCC, or clinical diagnosis of HCC as per AASLD criteria.
- BCLC stage B or C, and not suitable for curative surgical or local therapy.
- Participants have progressed on the prior first-line systemic treatment with atezolizumab plus bevacizumab combination treatment.
Key exclusion criteria (10 listed)
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- Tumor thrombus invasion of superior mesenteric vein.
- Has a known history of, or any evidence of CNS metastases.
- Has received anti-cancer therapy for HCC within 3 weeks prior to the first dose of study treatment.
- Has received systemic anti-cancer therapy other than atezolizumab and bevacizumab.
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 |
|---|---|---|
| AK104+lenvatinibSubjects will receive AK104+lenvatinib until disease progression | Biological | AK104+lenvatinib |
| lenvatinibSubjects will receive lenvatinib until disease progression | Drug | lenvatinib |
Primary outcome
Objective Response Rate (ORR) per RECIST v1.1 by Blinded Independent Central Review (BICR)
Time frame: Up to 24 months
Proportion of subjects who have a complete or partial response relative to baseline as assessed by BICR according to RECIST v1.1.
5 secondary outcomes
Overall Survival (OS)
Time frame: Up to 24 months
Progression-free survival (PFS) assessed by investigator per RECIST v1.1
Time frame: Up to 24 months
Duration of Response (DOR) assessed by investigator per RECIST v1.1
Time frame: Up to 24 months
Time to Response (TTR) assessed by investigator per RECIST v1.1
Time frame: Up to 24 months
Number of participants with adverse event (AE)
Time frame: Up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2025.
- 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.
Richard S. Finn, Ph.D. principal investigator
Department of Medicine, University of California
Jian Zhou, Ph.D. principal investigator
Fudan University
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AK104+lenvatinib and lenvatinib in people with HCC and Hepatocellular Carcinoma, run by Akeso.
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 10 inclusion and 10 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: opening soon, as of the sponsor's last update on 22 May 2025. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ting Liu, M.D. ((0760)89873999, clinicaltrials@akesobio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) per RECIST v1.1 by Blinded Independent Central Review (BICR) (time frame: Up to 24 months). 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 22 May 2025.