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

Primary Purpose

Hepatocellular Carcinoma

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AZD5851
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatocellular Carcinoma, Liver Cancer, Liver Neoplasm, advanced HCC, HCC, Metastatic Liver Cancer, CAR-T, CART, AZD5851, T-cell, Cell Therapy

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept 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).

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
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Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AZD5851

Arm Description

Subjects will receive AZD5851 following 3 consecutive doses of lymphodepleting chemotherapy (fludarabine and cyclophosphamide).

Outcomes

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
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)
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
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
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
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
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
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
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
Evaluation of the efficacy of the treatment by assessment of overall survival (OS)
9. Pharmacokinetics - maximum serum concentration of AZD5851
Maximum blood concentration (Cmax)
10. Pharmacokinetics -time to peak serum concentration of AZD5851
Time to peak (maximum) blood concentration (Tmax)
11. Pharmacokinetics -time to last measurable serum concentration of AZD5851
Time to last detectable blood concentration (Tlast)
12. Pharmacokinetics - Exposure of AZD5851
Area under the curve (AUC)

Full Information

First Posted
October 3, 2023
Last Updated
October 12, 2023
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT06084884
Brief Title
A Phase I/II Study to Evaluate AZD5851 in GPC3+ Advanced/Recurrent Hepatocellular Carcinoma
Acronym
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 Therapy Directed Against GPC3 in Adult Participants With Advanced/Recurrent HEpatocellular CarciNomA: ATHENA
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 18, 2023 (Anticipated)
Primary Completion Date
January 4, 2028 (Anticipated)
Study Completion Date
January 4, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Hepatocellular Carcinoma, Liver Cancer, Liver Neoplasm, advanced HCC, HCC, Metastatic Liver Cancer, CAR-T, CART, AZD5851, T-cell, Cell Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Masking Description
Open-label
Allocation
N/A
Enrollment
84 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
AZD5851
Arm Type
Experimental
Arm Description
Subjects will receive AZD5851 following 3 consecutive doses of lymphodepleting chemotherapy (fludarabine and cyclophosphamide).
Intervention Type
Biological
Intervention Name(s)
AZD5851
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Description
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
Time Frame
Through study completion, an average of 2 years
Secondary Outcome Measure Information:
Title
1. Proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR)
Description
Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1 (ORR)
Time Frame
Through study completion, an average of 2 years
Title
2. Interval between the date of AZD5851 infusion dose and first documented evidence of CR or PR
Description
Evaluation of the efficacy of the treatment by assessment of time to first response (TTR)
Time Frame
Through study completion, an average of 2 years
Title
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
Description
Evaluation of the efficacy of the treatment by assessment of disease control rate according to RECIST v1.1 (DCR)
Time Frame
Through study completion, an average of 2 years
Title
4. The proportion of participants who have a confirmed response (CR/PR) with a duration of at least a specific number of months
Description
Evaluation of the efficacy of the treatment by assessment of durable response rate according to RECIST v1.1 (DRR)
Time Frame
Through study completion, an average of 2 years
Title
5. The best response the participant achieved according to RECIST v1.1
Description
Evaluation of the efficacy of the treatment by assessment of best overall response according to RECIST v1.1 (BoR)
Time Frame
Through study completion, an average of 2 years
Title
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
Description
Evaluation of the efficacy of the treatment by assessment of duration of response according to RECIST v1.1 (DoR)
Time Frame
Through study completion, an average of 2 years
Title
7. Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause
Description
Evaluation of the efficacy of the treatment by assessment of progression-free survival (PFS)
Time Frame
Through study completion, an average of 2 years
Title
8. Interval between the date of first T cell infusion and date of death due to any cause
Description
Evaluation of the efficacy of the treatment by assessment of overall survival (OS)
Time Frame
Through study completion, an average of 2 years
Title
9. Pharmacokinetics - maximum serum concentration of AZD5851
Description
Maximum blood concentration (Cmax)
Time Frame
Through study completion, an average of 2 years
Title
10. Pharmacokinetics -time to peak serum concentration of AZD5851
Description
Time to peak (maximum) blood concentration (Tmax)
Time Frame
Through study completion, an average of 2 years
Title
11. Pharmacokinetics -time to last measurable serum concentration of AZD5851
Description
Time to last detectable blood concentration (Tlast)
Time Frame
Through study completion, an average of 2 years
Title
12. Pharmacokinetics - Exposure of AZD5851
Description
Area under the curve (AUC)
Time Frame
Through study completion, an average of 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
AstraZeneca Clinical Study Information Center
Phone
1-877-240-9479
Email
information.center@astrazeneca.com
Facility Information:
Facility Name
Research Site
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Research Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Research Site
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Research Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Research Site
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Research Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Research Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15237
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://vivli.org/

Learn more about this trial

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

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