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

Hepatocellular Carcinoma Clinical Trial

— ATHENA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06084884
• Other study ID #: D7670C00001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 27, 2023
• Est. completion date: December 13, 2027

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: December 13, 2027
• Est. primary completion date: December 13, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

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.

Locations

Country	Name	City	State
Korea, Republic of	Research Site	Seoul
United States	Research Site	Atlanta	Georgia
United States	Research Site	Columbus	Ohio
United States	Research Site	Duarte	California
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Jacksonville	Florida
United States	Research Site	New York	New York
United States	Research Site	Orange	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Rochester	Minnesota
United States	Research Site	San Francisco	California
United States	Research Site	Washington	District of Columbia
United States	Research Site	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	9. Pharmacokinetics - maximum serum concentration of AZD5851	Maximum blood concentration (Cmax)	Through study completion, an average of 2 years
Secondary	10. Pharmacokinetics -time to peak serum concentration of AZD5851	Time to peak (maximum) blood concentration (Tmax)	Through study completion, an average of 2 years
Secondary	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
Secondary	12. Pharmacokinetics - Exposure of AZD5851	Area under the curve (AUC)	Through study completion, an average of 2 years