What side effects are associated with this type of intervention?

Common treatments for liver cancer, such as sorafenib and CAR-GPC3 T-cells, often have side effects including elevated liver enzymes (ALT, AST), hyperbilirubinemia, and gastrointestinal issues like diarrhea and fatigue. Sorafenib specifically can cause hand-foot skin reactions, hypertension, and increased risk of bleeding. CAR-GPC3 T-cell therapy may lead to cytokine release syndrome, which can cause fever, fatigue, and hypotension. Close monitoring of liver function and overall health is essential during these treatments.

What prior FDA approvals exist?

The FDA has approved several targeted therapies and immunotherapies for the treatment of hepatocellular carcinoma (HCC). Sorafenib (Nexavar) was one of the first targeted therapies approved, acting as a multi-kinase inhibitor. Lenvatinib (Lenvima) is another tyrosine kinase inhibitor approved for first-line treatment of advanced HCC. Additionally, the combination of atezolizumab (an anti-PD-L1 antibody) and bevacizumab (an anti-VEGF antibody) has been approved based on the IMbrave150 trial, showing significant survival benefits. These treatments, like AZD5851, aim to target specific pathways involved in tumor growth and progression.

What other types of research exist?

Promising novel alternatives to AZD5851 for liver cancer patients include 20(S)-Ginsenoside Rg3, which inhibits autophagy and sensitizes HCC to doxorubicin, and evinacumab, a monoclonal antibody targeting ANGPTL3, which has shown efficacy in lowering LDL-C and may have potential applications in HCC treatment. Additionally, ongoing research into selective RET inhibitors like selpercatinib and pralsetinib, as well as FGFR inhibitors such as infigratinib and futibatinib, may offer new therapeutic options for liver cancer patients.

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Monoclonal Antibodies

AZD5851 for Liver Cancer (ATHENA Trial)

Phase 1 & 2

Recruiting

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Barcelona Clinic Liver Cancer Stage B (if not amenable to local treatment/surgery) or C prior to apheresis

Participants with confirmed advanced/recurrent or metastatic and/or unresectable HCC based on histopathological findings

Must not have

Uncontrolled intercurrent illness

History of chronic or recurrent (within the last year) severe autoimmune or immune mediated disease requiring steroids or other immune-suppressive treatments.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, an average of 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing AZD5851, a new drug, in adults with advanced liver cancer that has a specific marker (GPC3) and hasn't responded to other treatments. The drug aims to target and kill these specific cancer cells.

Who is the study for?

This trial is for adults with advanced or recurrent liver cancer (Hepatocellular Carcinoma) that can't be removed by surgery. Participants must have tried at least one standard treatment, have a specific protein on their tumor (GPC3+), and manage any hepatitis infections. They can't join if they've had HIV, liver transplant, certain blood vessel issues in the liver, severe illnesses or infections, recent hepatic encephalopathy, autoimmune diseases needing strong medication, previous CAR-T therapy targeting GPC3 or other treatments too close to the start of this trial.

What is being tested?

The study tests AZD5851 in patients with a particular type of liver cancer marked by GPC3+ proteins. It's an early-stage trial to see how safe it is and how well it works. The first phase checks for safety and dosage; the second phase assesses effectiveness against the disease.

What are the potential side effects?

While not specified here, typical side effects from similar cancer drugs may include nausea, fatigue, immune system reactions like fever or chills during infusion (infusion reactions), potential organ inflammation due to immune response activation and increased risk of infection.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My liver cancer is at an advanced stage and cannot be treated with surgery.

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My liver cancer cannot be removed by surgery and has spread.

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My tumor is GPC3 positive according to a specific lab test.

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My liver function is good.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any unmanaged ongoing illnesses.

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I have a severe autoimmune disease treated with steroids or other immune-suppressants in the last year.

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I have not had CAR-T therapy or treatments targeting GPC3.

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I do not have any active infections.

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I have fluid buildup in my abdomen that needs treatment.

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My cancer has spread to the main blood vessels near my liver.

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I have had a liver transplant or am on the waiting list for one.

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I received my last cancer treatment less than 21 days ago or within its 5 half-lives, whichever is shorter.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, an average of 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, an average of 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, an average of 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

1. Proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR)

10. Pharmacokinetics -time to peak serum concentration of AZD5851

11. Pharmacokinetics -time to last measurable serum concentration of AZD5851

+9 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: AZD5851Experimental Treatment1 Intervention

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

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for liver cancer include targeted therapies, immunotherapies, and locoregional treatments. Targeted therapies like AZD5851 focus on specific molecules such as glypican-3 (GPC3), which is overexpressed in hepatocellular carcinoma (HCC). By targeting GPC3, these therapies can inhibit tumor growth and induce cancer cell death. Immunotherapies, such as atezolizumab combined with bevacizumab, enhance the body's immune response against cancer cells. Locoregional treatments like TACE deliver chemotherapy directly to the liver tumor, minimizing systemic exposure and enhancing local efficacy. These mechanisms are crucial for liver cancer patients as they offer more precise and potentially effective treatment options, improving outcomes and reducing side effects compared to traditional chemotherapy.

Evaluation of antiglypican-3 therapy as a promising target for amelioration of hepatic tissue damage in hepatocellular carcinoma.