A Phase I/II Study to Evaluate AZD5851 in GPC3+ Advanced/Recurrent Hepatocellular Carcinoma (ATHENA)

August 18, 2026 updated by: AstraZeneca

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
94

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Japan
      • Kashiwa, Japan, 227-8577
        • Research Site
      • Osakasayama-shi, Japan, 589-8511
        • Research Site
  • South Korea
      • Seoul, South Korea, 03080
        • Research Site
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Research Site
    • California
      • Duarte, California, United States, 91010
        • Research Site
      • Los Angeles, California, United States, 90089
        • Research Site
      • Orange, California, United States, 92868
        • Research Site
      • San Francisco, California, United States, 94143
        • Research Site
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Research Site
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Research Site
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Research Site
    • Kansas
      • Westwood, Kansas, United States, 66205
        • Research Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Research Site
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Research Site
    • New York
      • New York, New York, United States, 10065
        • Research Site
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Research Site
    • Oregon
      • Portland, Oregon, United States, 97239
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Research Site
      • Pittsburgh, Pennsylvania, United States, 15237
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Participant must be 18 years or older and has voluntarily agreed to participate by giving written informed consent.
  2. Participants with confirmed advanced/recurrent or metastatic and/or unresectable HCC based on histopathological findings
  3. Completed or were unable to tolerate at least one prior line of standard systemic therapy for HCC and/or participant/investigator decision.
  4. GPC3-positive tumour as determined by a central laboratory using an analytically validated IHC assay
  5. Barcelona Clinic Liver Cancer Stage B (if not amenable to local treatment/surgery) or C prior to apheresis
  6. Child-Pugh score: Grade A
  7. Participants with HBV and HCV undergoing management of these infections per institutional practice.

Exclusion Criteria:

  1. Active or prior documented gastrointestinal (GI) variceal bleed or history of upper GI bleeding, ulcers, or esophageal varices with bleeding within 12 months
  2. History of liver transplantation or on waiting list
  3. Current clinically significant ascites
  4. Main portal vein thrombus, or tumor thrombus invasion of mesenteric vein / inferior vena cava
  5. Uncontrolled intercurrent illness
  6. Active Infections
  7. Positive serology for HIV
  8. History of hepatic encephalopathy within 12 months prior to treatment allocation
  9. History of chronic or recurrent (within the last year) severe autoimmune or immune mediated disease requiring steroids or other immune-suppressive treatments.
  10. Prior treatment with any CAR-T therapy directed at any target or any therapy that is targeted to GPC3.
  11. 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AZD5851
Subjects will receive AZD5851 following 3 consecutive doses of lymphodepleting chemotherapy (fludarabine and cyclophosphamide).
Biological: AZD5851

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.

Other Names:
  • Cell Therapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Through study completion, an average of 2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
1. Proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR)
Time Frame: Through study completion, an average of 2 years
Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1 (ORR)
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
Evaluation of the efficacy of the treatment by assessment of time to first response (TTR)
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
Evaluation of the efficacy of the treatment by assessment of disease control rate according to RECIST v1.1 (DCR)
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
Evaluation of the efficacy of the treatment by assessment of durable response rate according to RECIST v1.1 (DRR)
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
Evaluation of the efficacy of the treatment by assessment of best overall response according to RECIST v1.1 (BoR)
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
Evaluation of the efficacy of the treatment by assessment of duration of response according to RECIST v1.1 (DoR)
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
Evaluation of the efficacy of the treatment by assessment of progression-free survival (PFS)
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
Evaluation of the efficacy of the treatment by assessment of overall survival (OS)
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
Maximum blood concentration (Cmax)
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
Time to peak (maximum) blood concentration (Tmax)
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
Time to last detectable blood concentration (Tlast)
Through study completion, an average of 2 years
12. Pharmacokinetics - Exposure of AZD5851
Time Frame: Through study completion, an average of 2 years
Area under the curve (AUC)
Through study completion, an average of 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 14, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 13, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 13, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 3, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 12, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 16, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 19, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D7670C00001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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