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

AstraZeneca

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Hepatocellular Carcinoma

Treatments: Drug: AZD9793 Intravenous (IV) monotherapy; Drug: AZD9793 Subcutaneous (SC) monotherapy)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06795022

D7040C00001

Details and patient eligibility

About

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+.

Full 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).

Enrollment: 304 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.
• 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).
• Prior treatment with any therapy that is targeted to GPC3.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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304 participants in 2 patient groups

Module 1: AZD9793 Intravenous (IV) monotherapy

Experimental group

Description:

Module 1: AZD9793 Intravenous (IV) monotherapy

Treatment:

Drug: AZD9793 Intravenous (IV) monotherapy

Module 2: AZD9793 Subcutaneous (SC) monotherapy

Experimental group

Description:

Module 2: AZD9793 Subcutaneous (SC) monotherapy

Treatment:

Drug: AZD9793 Subcutaneous (SC) monotherapy)