AZD9793 for Liver Cancer

(RHEA-1 Trial)

Recruiting at 20 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disorders, CNS metastases, others

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

Compensation: Varies

Number of Visits: 2

304 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests AZD9793, a new antibody treatment, to determine its safety and effectiveness for liver cancer that cannot be removed or has spread. Researchers are examining how this treatment works when administered through an IV or as an injection under the skin. Suitable candidates have advanced liver cancer and have tried at least one other treatment without success. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have unresolved side effects from previous cancer treatments or if you have taken certain cancer therapies recently. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that AZD9793 is likely to be safe for humans?

Research has shown that AZD9793, a treatment designed to help immune cells attack cancer, is under study for safety in humans. In earlier studies, most patients experienced side effects, with about 97% reporting some level and 93.9% having side effects directly related to the treatment.

This treatment remains in the early stages of research. While no major safety issues have emerged so far, further studies are necessary to fully understand the risks. The treatment is being tested in two ways: intravenously and subcutaneously.

AZD9793 specifically targets a marker called GPC3, found on some liver cancer cells. This targeted approach might lead to fewer side effects compared to less specific cancer treatments. However, those considering joining a trial should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for liver cancer, which often include chemotherapy and targeted therapies like sorafenib, AZD9793 offers a novel approach. Researchers are excited about AZD9793 because it works differently by potentially targeting specific pathways in cancer cells, which could lead to more effective outcomes. Additionally, AZD9793 is being tested in two forms: as an intravenous (IV) monotherapy and as a subcutaneous (SC) monotherapy, offering flexibility in administration that could improve patient comfort and adherence. These unique features make AZD9793 a promising candidate in the battle against liver cancer.

What evidence suggests that AZD9793 could be an effective treatment for liver cancer?

Research has shown that AZD9793 could be a promising treatment for liver cancer. This experimental drug helps the immune system target a protein called GPC3, found on some cancer cells, including those in liver cancer. Studies have demonstrated that focusing on GPC3 can attack cancer cells specifically while sparing healthy cells, potentially reducing side effects. Early results indicate that AZD9793 can help T cells attack tumors, offering hope for its effectiveness against liver cancer. In this trial, researchers are testing both intravenous (through a vein) and subcutaneous (under the skin) forms of AZD9793 to determine the best method of administration. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals with advanced or metastatic solid tumors, specifically liver cancer or hepatocellular carcinoma. Participants must have tumors that test positive for a protein called GPC3.

Inclusion Criteria

My organs and bone marrow are functioning well.

I am following local guidelines for contraception as required.

Must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Exclusion Criteria

I have not had radiation in the last 14 days, except for specific palliative reasons.

My heart condition meets the study's requirements.

Participation in another clinical study with an investigational product administered in the last 21 days or 5 half-lives whichever is shorter prior to enrolment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive AZD9793 monotherapy intravenously or subcutaneously to determine the maximum tolerated dose

4-8 weeks

Weekly visits for dose adjustments and monitoring

Dose Expansion

Participants receive AZD9793 at the determined dose to further evaluate safety and efficacy

12 weeks

Bi-weekly visits for treatment and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Long-term Follow-up

Participants are monitored for long-term safety and survival outcomes

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• AZD9793

Trial Overview The study is testing AZD9793, an experimental antibody targeting the GPC3 protein on tumor cells. It's given as monotherapy either through IV (intravenous) or SC (subcutaneous) injections to evaluate safety, tolerability, and anti-cancer effects.

How Is the Trial Designed?

Group I: Module 2: AZD9793 Subcutaneous (SC) monotherapy Experimental Treatment 1 Intervention

Module 2: AZD9793 Subcutaneous (SC) monotherapy

Group II: Module 1: AZD9793 Intravenous (IV) monotherapy Experimental Treatment 1 Intervention

Module 1: AZD9793 Intravenous (IV) monotherapy

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/D7040C00001

First in human study to evaluate AZD9793 in participants ... This research is designed to determine if experimental treatment with AZD9793, a T cell-engaging antibody that targets GPC3, is safe, tolerable and has ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06795022

First in Human Study to Evaluate AZD9793 in Participants ... This research is designed to determine if experimental treatment with AZD9793, a T cell-engaging antibody that targets GPC3, is safe, tolerable and has anti- ...

3. researchgate.net researchgate.net/publication/392304574_RHEA-1_First-in-human_FIH_study_of_AZD9793_a_first-in-class_CD8-guided_T_cell-engager_TCE_for_glypican-3-positive_GPC3_advanced_or_metastatic_hepatocellular_carcinoma_HCC

First-in-human (FIH) study of AZD9793, a first-in-class CD8 ... Secondary endpoints include preliminary efficacy (only in dose escalation) in terms of response and progression-free survival by IA, as well as overall survival ...

4. onclive.com onclive.com/view/gpc3-offers-highly-specific-target-in-hcc

GPC3 Offers Highly Specific Target in HCC GPC3 has the potential to be targeted in patients with HCC with reduced off-target toxicities compared with other targeted agents.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12375816/

Targeting Glypican-3 for Liver Cancer Therapy Recent advancements in cancer immunotherapy have highlighted glypican-3 (GPC3) as a prominent target for treating hepatocellular carcinoma ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT485466

RHEA-1: First-in-human (FIH) study of AZD9793, a ... AZD9793, a trispecific IgG1 monoclonal antibody, is a first-in-class CD8-targeted TCE that directly engages tumor-infiltrating T cells and GPC3+ tumors, forming ...