AZD5851 for Liver Cancer

(ATHENA Trial)

Not currently recruiting at 23 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AstraZeneca

Must not be taking: Steroids, Immunosuppressants, CAR-T

Disqualifiers: HIV, Liver transplant, GI bleed, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AZD5851 for individuals with advanced or recurrent hepatocellular carcinoma (HCC). The goal is to evaluate AZD5851's effectiveness in patients whose tumors express the protein GPC3. Suitable candidates have inoperable liver cancer, have not responded to other treatments, and have tumors confirmed as GPC3-positive. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anticancer therapy at least 21 days before starting the study treatment, or within 5 half-lives of the medication, whichever is shorter. The protocol does not specify about other medications, so it's best to discuss with the trial team.

Is there any evidence suggesting that AZD5851 is likely to be safe for humans?

Research shows that AZD5851 is undergoing its first human trials to assess safety. The researchers have not yet determined how well people can tolerate it or what side effects might occur. As this study begins, the primary aim is to identify potential risks and observe patient responses to the treatment.

Early studies like this one focus on evaluating treatment safety. Although solid data is not yet available, results from this phase contribute to ensuring participant safety before broader use. Prospective participants should note that the current goal is to understand safety and treatment tolerance. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

AZD5851 is unique because it introduces a new approach to treating liver cancer by being used in conjunction with lymphodepleting chemotherapy, which is not common in current treatments. While most liver cancer treatments, like sorafenib or lenvatinib, target specific proteins involved in tumor growth, AZD5851 works differently by potentially enhancing the immune system's ability to fight the cancer. Researchers are excited about AZD5851 because it represents a novel strategy that could offer improved outcomes for patients by combining immune system activation with traditional chemotherapy methods.

What evidence suggests that AZD5851 might be an effective treatment for liver cancer?

Research has shown that AZD5851, a type of CAR-T therapy, may help treat liver cancer. CAR-T therapy modifies a person's immune cells to better attack cancer cells. Early results suggest that AZD5851 can shrink tumors. Initial studies indicate that similar treatments have worked in about 50% of liver cancer patients who have tried many other treatments, which is encouraging. Although human trial data remains limited, the mechanism of this therapy shows promise for those with advanced liver cancer. Participants in this trial will receive AZD5851 following lymphodepleting chemotherapy. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

I am over 18 and have agreed to join the study.

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

Exclusion Criteria

I do not have any unmanaged ongoing illnesses.

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

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive 3 consecutive doses of lymphodepleting chemotherapy (fludarabine and cyclophosphamide) before AZD5851 infusion

1 week

Treatment

Participants receive AZD5851, a CAR-T therapy directed against GPC3

2 years

Follow-up

Participants are monitored for safety, efficacy, and pharmacokinetics of AZD5851

2 years

What Are the Treatments Tested in This Trial?

Interventions

• AZD5851

Trial Overview 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.

How Is the Trial Designed?

Group I: AZD5851 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Citations

1. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7670C00001

A Phase I/II study to evaluate AZD5851 in GPC3+ ... This first-time in human, single-arm, open-label multicentre Phase I/II study will evaluate the safety, tolerability, antitumour activity, cellular kinetics, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06084884

NCT06084884 | A Phase I/II Study to Evaluate AZD5851 in ... This first-time in human, single-arm, open-label multicentre Phase I/II study will evaluate the safety, tolerability, antitumour activity, cellular kinetics ...

3. kucancercenter.org kucancercenter.org/cancer-clinical-trials/find-trial/clinical-trial-results/study00160163

A Phase I/II Open-Label Study to Evaluate the Safety ... 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 ...

4. alphaclinic.ucsf.edu alphaclinic.ucsf.edu/phase-iii-study-evaluate-azd5851-gpc3-advancedrecurrent-hepatocellular-carcinoma

A Phase I/II Study to Evaluate AZD5851 in GPC3+ Advanced ... This first-time in human, single-arm, open-label multicentre Phase I/II study will evaluate the safety, tolerability, anti-tumour activity, cellular kinetics, ...

5. oncologypipeline.com oncologypipeline.com/apexonco/asco-2024-preview-new-car-t-target-shows-liver-cancer-promise

ASCO 2024 preview – new Car-T target shows liver cancer ... C-CAR031 has shown a 50% confirmed response rate in its first-in-human study in the tough setting of heavily pretreated liver cancer, with no dose-limiting ...

6. mayo.edu mayo.edu/research/clinical-trials/cls-20569775

A Phase I/II Study to Evaluate AZD5851 in GPC3+ ... The purpose of this study is to evaluate AZD5851 in patients with GPC3+ advanced/recurrent hepatocellular carcinoma. Participation eligibility.