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

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: Active, not recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Biological: AZD5851

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: Interventional
• Enrollment (Estimated): 94
• Phase: Phase 2; Phase 1

Contacts and Locations

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
    • 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

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

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	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

Outcome Measure	Measure Description	Time Frame
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)	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)	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)	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)	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)	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)	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)	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)	Through study completion, an average of 2 years
9. Pharmacokinetics - maximum serum concentration of AZD5851	Maximum blood concentration (Cmax)	Through study completion, an average of 2 years
10. Pharmacokinetics -time to peak serum concentration of AZD5851	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 to last detectable blood concentration (Tlast)	Through study completion, an average of 2 years
12. Pharmacokinetics - Exposure of AZD5851	Area under the curve (AUC)	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2023
• Primary Completion (Estimated): December 13, 2027
• Study Completion (Estimated): December 13, 2027

Study Registration Dates

• First Submitted: October 3, 2023
• First Submitted That Met QC Criteria: October 12, 2023
• First Posted (Actual): October 16, 2023

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Hepatocellular Carcinoma; HCC; CAR-T; Liver Cancer; CART; Metastatic Liver Cancer; T-cell; Liver Neoplasm; advanced HCC; AZD5851
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms; Therapeutics; Biological Therapy; Cell- and Tissue-Based Therapy
• Other Study ID 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