Clinical trial NCT06084884: A Phase I/II Study to Evaluate AZD5851 in GPC3+ Advanced/Recurrent Hepatocellular Carcinoma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
Liver Cancer
Liver Neoplasm
advanced HCC
HCC
Metastatic Liver Cancer
CAR-T
CART
AZD5851
T-cell
Cell Therapy
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-10-16
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: 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
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
measure: 1. Proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR)
timeFrame: Through study completion, an average of 2 years
measure: 2. Interval between the date of AZD5851 infusion dose and first documented evidence of CR or PR
timeFrame: Through study completion, an average of 2 years
measure: 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
timeFrame: Through study completion, an average of 2 years
measure: 4. The proportion of participants who have a confirmed response (CR/PR) with a duration of at least a specific number of months
timeFrame: Through study completion, an average of 2 years
measure: 5. The best response the participant achieved according to RECIST v1.1
timeFrame: Through study completion, an average of 2 years
measure: 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
timeFrame: Through study completion, an average of 2 years
measure: 7. Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause
timeFrame: Through study completion, an average of 2 years
measure: 8. Interval between the date of first T cell infusion and date of death due to any cause
timeFrame: Through study completion, an average of 2 years
measure: 9. Pharmacokinetics - maximum serum concentration of AZD5851
timeFrame: Through study completion, an average of 2 years
measure: 10. Pharmacokinetics -time to peak serum concentration of AZD5851
timeFrame: Through study completion, an average of 2 years
measure: 11. Pharmacokinetics -time to last measurable serum concentration of AZD5851
timeFrame: Through study completion, an average of 2 years
measure: 12. Pharmacokinetics - Exposure of AZD5851
timeFrame: Through study completion, an average of 2 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Duarte
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Westwood
country: United States
facility: Research Site
state: Kansas
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: New York
country: United States
facility: Research Site
state: New York
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Chuo-ku
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Osakasayama-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
Study officials:
References: