First in Human Study to Evaluate AZD9793 in Participants With Advanced or Metastatic Solid Tumours (RHEA-1)

March 31, 2026 updated by: AstraZeneca

A Modular Phase I/II Open-label Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD9793, a T Cell-engaging Antibody Targeting Glypican-3 (GPC3) in Adult Participants With Advanced or Metastatic Solid Tumours (RHEA-1)

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-cancer activity in patients with advanced or metastatic solid tumours which are GPC3+.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a first-time in human, modular Phase I/II, open-label multicentre study of AZD9793 monotherapy administered intravenously (Module 1), or AZD9793 monotherapy administered subcutaneously (Module 2) in patients with advanced or metastatic solid tumours. Each module contains dose-escalation (Part A) and dose-expansion (Part B).

Study Type

Interventional

Enrollment (Estimated)

304

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Chengdu, China, 610041
        • Not yet recruiting
        • Research Site
      • Guangzhou, China, 510515
        • Recruiting
        • Research Site
      • Harbin, China, 150049
        • Not yet recruiting
        • Research Site
      • Shanghai, China, 201114
        • Recruiting
        • Research Site
  • Hong Kong
      • Pokfulam, Hong Kong, 999077
        • Not yet recruiting
        • Research Site
      • Shatin, Hong Kong, 000000
        • Recruiting
        • Research Site
  • Japan
      • Kashiwa, Japan, 277-8577
        • Recruiting
        • Research Site
      • Yokohama, Japan, 241-8515
        • Recruiting
        • Research Site
  • South Korea
      • Seoul, South Korea, 5505
        • Recruiting
        • Research Site
      • Seoul, South Korea, 06351
        • Not yet recruiting
        • Research Site
  • Spain
      • Barcelona, Spain, 8035
        • Not yet recruiting
        • Research Site
      • Pamplona, Spain, 31008
        • Not yet recruiting
        • Research Site
  • Taiwan
      • Taipei, Taiwan, 10002
        • Recruiting
        • Research Site
      • Taoyuan District, Taiwan, 333
        • Recruiting
        • Research Site
  • United States
    • California
      • La Jolla, California, United States, 92093
        • Not yet recruiting
        • Research Site
      • Los Angeles, California, United States, 90089
        • Not yet recruiting
        • Research Site
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Not yet recruiting
        • Research Site
    • Missouri
      • St Louis, Missouri, United States, 63108
        • Recruiting
        • Research Site
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Not yet recruiting
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Age ≥ 18 at the time of signing the informed consent.
  • GPC3 positive tumour as determined by a central laboratory using an analytically validated IHC assay. Patients who previously received any therapy targeting GPC3 must undergo central laboratory GPC3 testing on tumour tissue collected after completion of the prior GPC3-targeted therapy.
  • Must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • Eastern Cooperative Oncology Group Performance status (ECOG PS): 0-1 at screening.
  • Predicted life expectancy of ≥ 12 weeks.
  • Adequate organ and bone marrow function measured within 28 days prior to first dose as defined by the protocol.
  • Contraceptive use by men or women should be consistent with local regulations, as defined by the protocol.
  • Confirmed advanced recurrent and/or metastatic and/or unresectable HCC, which is histopathologically proven based on the criteria established by the World Health Organization.
  • Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C.
  • Child-Pugh Score class A.
  • Previous therapy:

Part A: Patients who have received at least one prior line of standard systemic therapy for HCC as per National Comprehensive Cancer Network or other local scientific guidelines and for which a clinical study is the best option for next treatment based on prior response and/or tolerability and/or patient/investigator decision.

Part B: Patients must not have received more than one prior line of systemic therapy in the advanced recurrent and/or metastatic setting.

Key Exclusion Criteria:

  • Unresolved toxicity from prior anticancer therapy, including imAEs, of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 except for vitiligo, peripheral neuropathy related to prior anti-cancer therapy, alopecia, endocrine disorders that are controlled with replacement hormone therapy and asymptomatic laboratory abnormalities.
  • Prior to enrolment, participation in another clinical study with an investigational product administered in the last 21 days or 5 half-lives whichever is shorter.
  • CAR-T cell therapy within the last 6 months prior to enrolment on this study.
  • Known allergy or hypersensitivity to AZD9793 or any of the excipients of the product as outlined in the IB.
  • Requires chronic immunosuppressive therapy (including steroids > 10 mg prednisone/day or equivalent).
  • Received radiation within 14 days prior to first dose of study treatment; palliative radiation to reduce the risk of tumour lysis syndrome (TLS) or CRS/neurotoxicity in participants with bulky disease is permitted.
  • Undergone a major surgical procedure within 14 days prior to first dose of study treatment days to allow adequate healing
  • Experienced unacceptable cytokine release syndrome (CRS) or Immune Effector Cell Associated Neurotoxicity (ICANS) following prior T cell engagers (TCE) or chimeric antigen receptor T (CAR-T) cell therapy.
  • Previous history of hemophagocytic lymphohistiocytosis (HLH) / macrophage activation syndrome (MAS).
  • Active or prior documented autoimmune or inflammatory disorders within 3 years of start of treatment.
  • Cardiac conditions as defined by the protocol.
  • History of thromboembolic event within the past 3 months prior to the scheduled first dose of study intervention.
  • Central nervous system (CNS) metastases or CNS pathology, as defined by the protocol, within 3 months prior to consent.
  • Infectious disease including active human immunodeficiency virus (HIV), and uncontrolled active systemic fungal, bacterial or other infection.
  • Known fibrolamellar HCC, sarcomatoid HCC, or combined hepatocellular malignant cholangiocarcinoma.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Module 1: AZD9793 Intravenous (IV) monotherapy Part A
Module 1: AZD9793 Intravenous (IV) monotherapy Part A: Dose Escalation
Drug: AZD9793 Intravenous (IV) monotherapy
T cell-engaging antibody that targets GPC3 on tumour cells
Experimental: Module 2: AZD9793 Subcutaneous (SC) monotherapy Part A
Module 2: AZD9793 Subcutaneous (SC) monotherapy Part A: Dose Escalation
Drug: AZD9793 Subcutaneous (SC) monotherapy
T cell-engaging antibody that targets GPC3 on tumour cells
Experimental: Module 1: AZD9793 Intravenous (IV) monotherapy Part B
Module 1: AZD9793 Intravenous (IV) monotherapy Part B: Dose Expansion
Drug: AZD9793 Intravenous (IV) monotherapy
T cell-engaging antibody that targets GPC3 on tumour cells
Experimental: Module 2: AZD9793 Subcutaneous (SC) monotherapy Part B
Module 2: AZD9793 Subcutaneous (SC) monotherapy Part B: Dose Expansion
Drug: AZD9793 Subcutaneous (SC) monotherapy
T cell-engaging antibody that targets GPC3 on tumour cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of patients with adverse events
Time Frame: From first dose of study drug up to 30 days post last dose and prior to start of subsequent anticancer therapy
Number of patients with adverse events by system organ class and preferred term
From first dose of study drug up to 30 days post last dose and prior to start of subsequent anticancer therapy
The number of patients with serious adverse events
Time Frame: From first dose of study drug up to 30 days post last dose and prior to start of subsequent anticancer therapy
Number of patients with serious adverse events by system organ class and preferred term
From first dose of study drug up to 30 days post last dose and prior to start of subsequent anticancer therapy
The number of patients with adverse events of special interest
Time Frame: From first dose of study drug up to 30 days post last dose and prior to start of subsequent anticancer therapy
Number of patients with adverse events of special interest by system organ class and preferred term
From first dose of study drug up to 30 days post last dose and prior to start of subsequent anticancer therapy
The number of AEs leading to discontinuation of AZD9793
Time Frame: From first dose of study drug up to 30 days post last dose and prior to start of subsequent anticancer therapy
Number of AEs that in the opinion of the Investigator or the Sponsor contraindicate further dosing or AEs that meet criteria for discontinuation
From first dose of study drug up to 30 days post last dose and prior to start of subsequent anticancer therapy
The number of patients with dose-limiting toxicity (DLT), as defined in the protocol [Part A Dose Escalation only]
Time Frame: From date of first dose of study drug until the end of DLT evaluation period (up to 21, 28 or 35 days depending on dose regimen)
Number of patients with at least 1 DLT. A DLT is a toxicity as defined in the protocol that occurs from the first dose of study drug up to and including the planned end of the DLT evaluation period that is assessed as unrelated to the disease or disease-related processes under investigation.
From date of first dose of study drug until the end of DLT evaluation period (up to 21, 28 or 35 days depending on dose regimen)
Objective Response Rate (ORR) [Part B Dose Expansion only]
Time Frame: From first dose of study drug to progressive disease or the last evaluable assessment in the absence of disease progression whichever comes first (up to approximately 2 years)
The percentage of patients with a confirmed investigator assessed complete or partial response according to response criteria in solid tumours (RECIST 1.1). Dose expansion only.
From first dose of study drug to progressive disease or the last evaluable assessment in the absence of disease progression whichever comes first (up to approximately 2 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best overall response (BOR)
Time Frame: From first dose until disease progression or the last evaluable assessment in the absence of progression (up to approximately 2 years)
The best overall radiological visit response the participant achieves per RECIST 1.1 as assessed by the investigator.
From first dose until disease progression or the last evaluable assessment in the absence of progression (up to approximately 2 years)
Disease Control Rate (DCR) at 12 weeks
Time Frame: From first dose of study drug to progressive disease or last evaluable assessment in the absence of disease progression. [Expected to be measured for each patient at 12 weeks]
Percentage of patients with confirmed complete or partial response or having stable disease maintained for >= 11 weeks, at 12 weeks from first dose, according to response criteria in solid tumours (RECIST 1.1).
From first dose of study drug to progressive disease or last evaluable assessment in the absence of disease progression. [Expected to be measured for each patient at 12 weeks]
Durable response rate (DRR)
Time Frame: From first documented objective response (subsequently confirmed) to the date of disease progression or the last evaluable assessment in the absence of progression (up to approximately 2 years)
Percentage of participants who have a confirmed best overall response of CR or PR with a duration of at least 3 months, 6 months, 9 months, and 12 months.
From first documented objective response (subsequently confirmed) to the date of disease progression or the last evaluable assessment in the absence of progression (up to approximately 2 years)
Duration of response (DoR)
Time Frame: From the first documented objective response (subsequently confirmed) to progressive disease or death in absence of progression (up to approximately 2 years)
The time from the date of first response until date of disease progression or death in the absence of disease progression, according to response criteria in solid tumours (RECIST 1.1).
From the first documented objective response (subsequently confirmed) to progressive disease or death in absence of progression (up to approximately 2 years)
Time To Response (TTR)
Time Frame: From start of study treatment until the date of first documented objective response, which is subsequently confirmed as assessed by the Investigator per RECIST 1.1 (up to approximately 2 years)
The time from start of study treatment until the date of first documented objective response, which is subsequently confirmed as assessed by the Investigator per RECIST 1.1.
From start of study treatment until the date of first documented objective response, which is subsequently confirmed as assessed by the Investigator per RECIST 1.1 (up to approximately 2 years)
Progression free Survival (PFS)
Time Frame: From the start of study treatment to progressive disease or death due to any cause (up to approximately 2 years)
The time from the start of study treatment until RECIST 1.1 defined disease progression or death in the absence of disease progression.
From the start of study treatment to progressive disease or death due to any cause (up to approximately 2 years)
Overall Survival (OS) [Dose expansion only]
Time Frame: From the start of study treatment to death (up to approximately 2 years)
The time from the start of study treatment until death due to any cause. Dose expansion only.
From the start of study treatment to death (up to approximately 2 years)
Pharmacokinetics of AZD9793: Maximum serum concentration of the study drug (Cmax)
Time Frame: From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years)
Maximum observed serum concentration of the study drug
From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years)
Pharmacokinetics of AZD9793: Area Under the concentration-time curve (AUC)
Time Frame: From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years)
Area under the serum concentration-time curve
From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years)
Pharmacokinetics of AZD9793: Clearance
Time Frame: From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years)
A pharmacokinetic measurement of the volume of serum from which the study drug is completely removed per unit time.
From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years)
Pharmacokinetics of AZD9793: Terminal elimination half-life (t 1/2)
Time Frame: From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years)
Terminal elimination half life.
From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years)
Immunogenicity of AZD9793
Time Frame: From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years)
The number and percentage of participants who develop anti-drug antibodies (ADAs) measured in serum
From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years)
Change in CD8+ Levels
Time Frame: From time of Informed consent, at predefined intervals (including screening, on-treatment or end of treatment) throughout the study (up to approximately 2 years)
Percentage change in CD8+ cells measured by IHC in samples taken pre and post treatment
From time of Informed consent, at predefined intervals (including screening, on-treatment or end of treatment) throughout the study (up to approximately 2 years)
Objective Response Rate (ORR) [Part A Dose Escalation only]
Time Frame: From first dose of study drug to progressive disease or the last evaluable assessment in the absence of disease progression whichever comes first (up to approximately 2 years)
The percentage of patients with a confirmed investigator assessed complete or partial response according to response criteria in solid tumours (RECIST 1.1). Dose escalation only.
From first dose of study drug to progressive disease or the last evaluable assessment in the absence of disease progression whichever comes first (up to approximately 2 years)
Percentage change in tumour size
Time Frame: From first dose of study drug to the last evaluable assessment
Percentage change from baseline in target lesion tumour size (sum of longest diameters of target lesions) based on the RECIST v1.1 target lesion measurements as assessed by the Investigator.
From first dose of study drug to the last evaluable assessment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 27, 2025

Primary Completion (Estimated)

February 25, 2028

Study Completion (Estimated)

July 25, 2028

Study Registration Dates

First Submitted

January 8, 2025

First Submitted That Met QC Criteria

January 24, 2025

First Posted (Actual)

January 27, 2025

Study Record Updates

Last Update Posted (Actual)

April 6, 2026

Last Update Submitted That Met QC Criteria

March 31, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D7040C00001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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 shared.

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 rerefer 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. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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