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

Sponsor

AstraZeneca (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06084884

Collaborator

(none)

Enrollment

Locations

Arm

48.6

Anticipated Duration (Months)

8.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase I/II study to evaluate AZD5851 in patients with GPC3+ advanced/recurrent hepatocellular carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Biological: AZD5851	Phase 1/Phase 2

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

Study Type:

Interventional

Anticipated Enrollment :

84 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Masking Description:

Open-label

Primary Purpose:

Treatment

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 Therapy Directed Against GPC3 in Adult Participants With Advanced/Recurrent HEpatocellular CarciNomA: ATHENA

Anticipated Study Start Date :

Dec 18, 2023

Anticipated Primary Completion Date :

Jan 4, 2028

Anticipated Study Completion Date :

Jan 4, 2028

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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 [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

Secondary Outcome Measures

1. Proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR) [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)
2. Interval between the date of AZD5851 infusion dose and first documented evidence of CR or PR [Through study completion, an average of 2 years]
Evaluation of the efficacy of the treatment by assessment of time to first response (TTR)
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 [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)
4. The proportion of participants who have a confirmed response (CR/PR) with a duration of at least a specific number of months [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)
5. The best response the participant achieved according to RECIST v1.1 [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)
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 [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)
7. Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause [Through study completion, an average of 2 years]
Evaluation of the efficacy of the treatment by assessment of progression-free survival (PFS)
8. Interval between the date of first T cell infusion and date of death due to any cause [Through study completion, an average of 2 years]
Evaluation of the efficacy of the treatment by assessment of overall survival (OS)
9. Pharmacokinetics - maximum serum concentration of AZD5851 [Through study completion, an average of 2 years]
Maximum blood concentration (Cmax)
10. Pharmacokinetics -time to peak serum concentration of AZD5851 [Through study completion, an average of 2 years]
Time to peak (maximum) blood concentration (Tmax)
11. Pharmacokinetics -time to last measurable serum concentration of AZD5851 [Through study completion, an average of 2 years]
Time to last detectable blood concentration (Tlast)
12. Pharmacokinetics - Exposure of AZD5851 [Through study completion, an average of 2 years]
Area under the curve (AUC)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 130 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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
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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Duarte	California	United States	91010
2	Research Site	San Francisco	California	United States	94143
3	Research Site	Westwood	Kansas	United States	66205
4	Research Site	Rochester	Minnesota	United States	55905
5	Research Site	Hackensack	New Jersey	United States	07601
6	Research Site	New York	New York	United States	10065
7	Research Site	Columbus	Ohio	United States	43210
8	Research Site	Portland	Oregon	United States	97239
9	Research Site	Philadelphia	Pennsylvania	United States	19104
10	Research Site	Pittsburgh	Pennsylvania	United States	15237