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

Phase 1

Recruiting

• Conditions: Hepatocellular Carcinoma
• Interventions: Drug: AZD9793 Intravenous (IV) monotherapy; Drug: AZD9793 Subcutaneous (SC) monotherapy)

• Registration Number: NCT06795022
• Lead Sponsor: AstraZeneca

Brief Summary

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+.

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 Timeline

• Study First Submitted: 2025-01-08
• Study First Submitted QC: 2025-01-24
• Study First Posted: 2025-01-27
• Study Start: 2025-03-27
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-09
• Last Update Posted: 2025-04-11
• Primary Completion: 2028-02-28
• Study Completion: 2028-07-27

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 304

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.
• 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 NCCN 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 1 prior line of systemic therapy in the advanced recurrent and/or metastatic setting.

Key

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Module 1: AZD9793 Intravenous (IV) monotherapy	AZD9793 Intravenous (IV) monotherapy	Module 1: AZD9793 Intravenous (IV) monotherapy
Module 2: AZD9793 Subcutaneous (SC) monotherapy	AZD9793 Subcutaneous (SC) monotherapy)	Module 2: AZD9793 Subcutaneous (SC) monotherapy

Primary Outcome Measures

Name	Time	Method
The number of patients with adverse events	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
The number of patients with serious adverse events	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
The number of patients with adverse events of special interest	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
The number of patients with dose-limiting toxicity (DLT), as defined in the protocol.	From date of first dose of study drug until the end of Cycle 1 (up to 28 days)	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 Cycle 1 (the DLT assessment period) that is assessed as unrelated to the disease or disease-related processes under investigation.
Objective Response Rate (ORR) [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)	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.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) [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)	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.
Best overall response (BOR)	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.
Disease Control Rate (DCR) at 12 weeks	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).
Durable response rate (DRR)	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.
Duration of response (DoR)	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).
Time To Response (TTR)	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.
Progression free Survival (PFS)	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.
Overall Survival (OS) [Dose expansion only]	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.
Pharmacokinetics of AZD9793: Maximum serum concentration of the study drug (Cmax)	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
Pharmacokinetics of AZD9793: Area Under the concentration-time curve (AUC)	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
Pharmacokinetics of AZD9793: Clearance	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.
Pharmacokinetics of AZD9793: Terminal elimination half-life (t 1/2)	From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years)	Terminal elimination half life.
Immunogenicity of AZD9793	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
Change in CD8+ Levels	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

Trial Locations

Locations (1)

Research Site; 🇰🇷 Seoul, Korea, Republic of