RECRUITING

First in Human Study to Evaluate AZD9793 in Participants With Advanced or Metastatic Solid Tumours

Conditions

Hepatocellular Carcinoma Glypican-3 GPC3 GPC3+ tumours T cell-engaging antibody TCE AZD9793 Solid tumours HCC

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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+.

Official Title

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)

Quick Facts

Study Start:2025-03-27

Study Completion:2028-07-27

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06795022

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. * 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:	* Unresolved toxicity from prior anticancer therapy, including irAEs, 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). * Prior treatment with any therapy that is targeted to GPC3. * Received any therapy to treat cancer (including chemotherapy, biologics, cellular therapies) within 5 half-lives of an anticancer drug prior to the first dose of study treatment. * Received radiation within 14 days; 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 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.

Inclusion Criteria

Exclusion 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.
* 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:

* Unresolved toxicity from prior anticancer therapy, including irAEs, 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).
* Prior treatment with any therapy that is targeted to GPC3.
* Received any therapy to treat cancer (including chemotherapy, biologics, cellular therapies) within 5 half-lives of an anticancer drug prior to the first dose of study treatment.
* Received radiation within 14 days; 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 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.

Contacts and Locations

Study Contact

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479

information.center@astrazeneca.com

Study Locations (Sites)

Research Site

Saint Louis, Missouri, 63110

United States

Research Site

Houston, Texas, 77030

United States

Collaborators and Investigators

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 Registration Dates

Study Start Date2025-03-27

Study Completion Date2028-07-27

Study Record Updates

Study Start Date2025-03-27

Study Completion Date2028-07-27

Terms related to this study

Keywords Provided by Researchers

Glypican-3
GPC3
GPC3+ tumours
T cell-engaging antibody
TCE
AZD9793
Solid tumours
HCC

Additional Relevant MeSH Terms

Hepatocellular Carcinoma