Hepatocellular CarcinomaPhase 1/2ATHENANCT06084884
A Phase I/II Study to Evaluate AZD5851 in GPC3+ Advanced/Recurrent Hepatocellular Carcinoma
A Phase 1/2 study testing AZD5851 in people with Hepatocellular Carcinoma, run by AstraZeneca at 19 sites in 3 countries.
Trial summary
A Phase I/II study to evaluate AZD5851 in patients with GPC3+ advanced/recurrent hepatocellular carcinoma. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- AZD5851
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 19 sitesin 3 countries
- Study dates
- 14 Dec 2023to 13 Dec 2027
- Phase
- Phase 1/2
- 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 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must be 18 years or older and has voluntarily agreed to participate by giving written informed consent.
- Participants with confirmed advanced/recurrent or metastatic and/or unresectable HCC based on histopathological findings
- Completed or were unable to tolerate at least one prior line of standard systemic therapy for HCC and/or participant/investigator decision.
- GPC3-positive tumour as determined by a central laboratory using an analytically validated IHC assay
- Barcelona Clinic Liver Cancer Stage B (if not amenable to local treatment/surgery) or C prior to apheresis
- Child-Pugh score: Grade A
- Participants with HBV and HCV undergoing management of these infections per institutional practice.
Who cannot join
- Active or prior documented gastrointestinal (GI) variceal bleed or history of upper GI bleeding, ulcers, or esophageal varices with bleeding within 12 months
- History of liver transplantation or on waiting list
- Current clinically significant ascites
- Main portal vein thrombus, or tumor thrombus invasion of mesenteric vein / inferior vena cava
- Uncontrolled intercurrent illness
- Active Infections
Show all 11Show fewer
- Positive serology for HIV
- History of hepatic encephalopathy within 12 months prior to treatment allocation
- History of chronic or recurrent (within the last year) severe autoimmune or immune mediated disease requiring steroids or other immune-suppressive treatments.
- Prior treatment with any CAR-T therapy directed at any target or any therapy that is targeted to GPC3.
- Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolisation, or monoclonal antibodies, investigational product) within 5 half-lives or ≤ 21 days (whichever is shortest).
Trial locations and contacts
19 sites in 3 countries.
19 sites in 3 countries
United States16 sites
Research Site
Atlanta, Georgia, 30322
Research Site
Columbus, Ohio, 43210
Research Site
Duarte, California, 91010
Research Site
Hackensack, New Jersey, 07601
Research Site
Jacksonville, Florida, 32224
Research Site
Los Angeles, California, 90089
Research Site
New York, New York, 10065
Research Site
Orange, California, 92868
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Phoenix, Arizona, 85054
Research Site
Pittsburgh, Pennsylvania, 15237
Research Site
Portland, Oregon, 97239
Research Site
Rochester, Minnesota, 55905
Research Site
San Francisco, California, 94143
Research Site
Washington D.C., District of Columbia, 20007
Research Site
Westwood, Kansas, 66205
Japan2 sites
Research Site
Kashiwa, 227-8577
Research Site
Osakasayama-shi, 589-8511
About this study
Official title: A Phase I/II Open-Label Study to Evaluate the Safety, Cellular Kinetics and Efficacy of AZD5851, a Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Directed Against GPC3 in Adult Participants With Advanced/Recurrent Hepatocellular Carcinoma: ATHENA
A Phase I/II study to evaluate AZD5851 in patients with GPC3+ advanced/recurrent hepatocellular carcinoma.
Read the detailed description
This first-time in human, single-arm, open-label multicentre Phase I/II study will evaluate the safety, tolerability, antitumour activity, cellular kinetics, pharmacodynamics, and immunogenicity of AZD5851 in adult participants with GPC3+ advanced/recurrent HCC, where at least one line of prior therapy has failed/or was intolerable, or participant/investigator decision.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- AZD5851
- Keywords
- Hepatocellular Carcinoma, Liver Cancer, Liver Neoplasm, advanced HCC, HCC, Metastatic Liver Cancer, CAR-T, CART, AZD5851, T-cell, Cell Therapy
- Medical subject headings
- Carcinoma, Hepatocellular, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD5851Biological
Also called Cell Therapy
Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) to produce AZD5851.
During AZD5851 production, subjects may receive bridging therapy for disease control. Upon successful generation of AZD5851 product, subjects will receive treatment with AZD5851 therapy.
Study treatment will include lymphodepleting chemotherapy followed by one dose of AZD5851 administered by intravenous (IV) infusion.
| Study group | Role | What they receive |
|---|---|---|
| AZD5851 | Experimental | Subjects will receive AZD5851 following 3 consecutive doses of lymphodepleting chemotherapy (fludarabine and cyclophosphamide). Receives: Biological: AZD5851 |
What is being measured
The primary outcome is the main question the study is designed to answer.
1. Incidence of participants with dose-limiting toxicities (DLTs), adverse events (AEs), including adverse events of special interest (AESI) and serious adverse events (SAEs). Determination of the recommended dose of AZD5851 for expansion phase
Determine if treatment with AZD5851 is safe and tolerable through assessment of DLTs, AEs, SAEs and changes from baseline in vital signs, ECGs, and laboratory parameters
Measured: Through study completion, an average of 2 years
Secondary outcomes (12)
1. Proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR)
Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1 (ORR)
Measured: Through study completion, an average of 2 years
2. Interval between the date of AZD5851 infusion dose and first documented evidence of CR or PR
Evaluation of the efficacy of the treatment by assessment of time to first response (TTR)
Measured: Through study completion, an average of 2 years
3. Proportion of participants who have a confirmed CR, PR, or who have stable disease (SD) for at least 5 weeks after the date of AZD5851 infusion
Evaluation of the efficacy of the treatment by assessment of disease control rate according to RECIST v1.1 (DCR)
Measured: Through study completion, an average of 2 years
4. The proportion of participants who have a confirmed response (CR/PR) with a duration of at least a specific number of months
Evaluation of the efficacy of the treatment by assessment of durable response rate according to RECIST v1.1 (DRR)
Measured: Through study completion, an average of 2 years
5. The best response the participant achieved according to RECIST v1.1
Evaluation of the efficacy of the treatment by assessment of best overall response according to RECIST v1.1 (BoR)
Measured: Through study completion, an average of 2 years
6. Interval between the date of first documented objective response date of first documented disease progression or the last evaluable assessment in the absence of progression
Evaluation of the efficacy of the treatment by assessment of duration of response according to RECIST v1.1 (DoR)
Measured: Through study completion, an average of 2 years
7. Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause
Evaluation of the efficacy of the treatment by assessment of progression-free survival (PFS)
Measured: Through study completion, an average of 2 years
8. Interval between the date of first T cell infusion and date of death due to any cause
Evaluation of the efficacy of the treatment by assessment of overall survival (OS)
Measured: Through study completion, an average of 2 years
9. Pharmacokinetics - maximum serum concentration of AZD5851
Maximum blood concentration (Cmax)
Measured: Through study completion, an average of 2 years
10. Pharmacokinetics -time to peak serum concentration of AZD5851
Time to peak (maximum) blood concentration (Tmax)
Measured: Through study completion, an average of 2 years
11. Pharmacokinetics -time to last measurable serum concentration of AZD5851
Time to last detectable blood concentration (Tlast)
Measured: Through study completion, an average of 2 years
12. Pharmacokinetics - Exposure of AZD5851
Area under the curve (AUC)
Measured: Through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2023
- Study start14 Dec 2023
- Primary completion13 Dec 2027 (estimated)
- Study completion13 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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
- 94 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06084884
- Sponsor's protocol ID
- D7670C00001
- Acronym
- ATHENA
- Status last verified
- Aug 2026
- First submitted
- 3 Oct 2023
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Open-Label Study to Evaluate the Safety, Cellular Kinetics and Efficacy of AZD5851, a Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Directed Against GPC3 in Adult Participants With Advanced/Recurrent Hepatocellular Carcinoma: ATHENA
- ClinicalTrials.gov ID
- NCT06084884
- Acronym / sponsor ID
- ATHENA / D7670C00001
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular Carcinoma, Liver Cancer, Liver Neoplasm, advanced HCC, HCC, Metastatic Liver Cancer, CAR-T, CART
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 94 participants (estimated)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 14 Dec 2023 (actual)
- Primary completion
- 13 Dec 2027 (estimated)
- Study completion
- 13 Dec 2027 (estimated)
- First posted
- 16 Oct 2023 (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.
A Phase I/II study to evaluate AZD5851 in patients with GPC3+ advanced/recurrent hepatocellular carcinoma.
Detailed description
This first-time in human, single-arm, open-label multicentre Phase I/II study will evaluate the safety, tolerability, antitumour activity, cellular kinetics, pharmacodynamics, and immunogenicity of AZD5851 in adult participants with GPC3+ advanced/recurrent HCC, where at least one line of prior therapy has failed/or was intolerable, or participant/investigator decision.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AZD5851 | Experimental | Biological: AZD5851Subjects will receive AZD5851 following 3 consecutive doses of lymphodepleting chemotherapy (fludarabine and cyclophosphamide). |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Participant must be 18 years or older and has voluntarily agreed to participate by giving written informed consent.
- Participants with confirmed advanced/recurrent or metastatic and/or unresectable HCC based on histopathological findings
- Completed or were unable to tolerate at least one prior line of standard systemic therapy for HCC and/or participant/investigator decision.
- GPC3-positive tumour as determined by a central laboratory using an analytically validated IHC assay
- Barcelona Clinic Liver Cancer Stage B (if not amenable to local treatment/surgery) or C prior to apheresis
Key exclusion criteria (11 listed)
- Active or prior documented gastrointestinal (GI) variceal bleed or history of upper GI bleeding, ulcers, or esophageal varices with bleeding within 12 months
- History of liver transplantation or on waiting list
- Current clinically significant ascites
- Main portal vein thrombus, or tumor thrombus invasion of mesenteric vein / inferior vena cava
- Uncontrolled intercurrent illness
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 |
|---|---|---|
| AZD5851Also: Cell TherapySubjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) to produce AZD5851. During AZD5851 production, subjects may receive bridging therapy for disease control. Upon successful generation of AZD5851 product, subjects will receive treatment with AZD5851 therapy. Study treatment will include lymphodepleting chemotherapy followed by one dose of AZD5851 administered by intravenous (IV) infusion. | Biological | AZD5851 |
Primary outcome
1. Incidence of participants with dose-limiting toxicities (DLTs), adverse events (AEs), including adverse events of special interest (AESI) and serious adverse events (SAEs). Determination of the recommended dose of AZD5851 for expansion phase
Time frame: Through study completion, an average of 2 years
Determine if treatment with AZD5851 is safe and tolerable through assessment of DLTs, AEs, SAEs and changes from baseline in vital signs, ECGs, and laboratory parameters
12 secondary outcomes
1. Proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR)
Time frame: Through study completion, an average of 2 years
2. Interval between the date of AZD5851 infusion dose and first documented evidence of CR or PR
Time frame: Through study completion, an average of 2 years
3. Proportion of participants who have a confirmed CR, PR, or who have stable disease (SD) for at least 5 weeks after the date of AZD5851 infusion
Time frame: Through study completion, an average of 2 years
4. The proportion of participants who have a confirmed response (CR/PR) with a duration of at least a specific number of months
Time frame: Through study completion, an average of 2 years
5. The best response the participant achieved according to RECIST v1.1
Time frame: Through study completion, an average of 2 years
6. Interval between the date of first documented objective response date of first documented disease progression or the last evaluable assessment in the absence of progression
Time frame: Through study completion, an average of 2 years
7. Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause
Time frame: Through study completion, an average of 2 years
8. Interval between the date of first T cell infusion and date of death due to any cause
Time frame: Through study completion, an average of 2 years
9. Pharmacokinetics - maximum serum concentration of AZD5851
Time frame: Through study completion, an average of 2 years
10. Pharmacokinetics -time to peak serum concentration of AZD5851
Time frame: Through study completion, an average of 2 years
11. Pharmacokinetics -time to last measurable serum concentration of AZD5851
Time frame: Through study completion, an average of 2 years
12. Pharmacokinetics - Exposure of AZD5851
Time frame: Through study completion, an average of 2 years
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 19 Aug 2026.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
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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.
The record lists no contact. Use the official record to reach the sponsor.
19 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZD5851 in people with Hepatocellular Carcinoma, run by AstraZeneca at 19 sites in 3 countries.
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 7 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Japan, South Korea. 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?
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?
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?
1. Incidence of participants with dose-limiting toxicities (DLTs), adverse events (AEs), including adverse events of special interest (AESI) and serious adverse events (SAEs). Determination of the recommended dose of AZD5851 for expansion phase (time frame: Through study completion, an average of 2 years). 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 19 Aug 2026.