Esophageal Adenocarcinoma, Gastric Cancer, Gastro-esophageal Junction Cancer, Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
CLDN18.2 / Claudin 18.2, CD3, T cell-engaging bi-specific antibody, Gastric cancer, Gastro-esophageal junction cancer, Pancreatic ductal adenocarcinoma, Solid tumors, AZD5863
Brief summary
This research is designed to determine if experimental treatment with AZD5863, a T cell-engaging bispecific antibody that targets Claudin 18.2 (CLDN18.2) and CD3, is safe, tolerable and has anti-cancer activity in patients with advanced solid tumors.
Detailed description
This is a first-time in human, modular Phase I/II, open-label multicentre study of AZD5863 monotherapy administered intravenously (Module 1), or AZD5863 monotherapy administered subcutaneously (Module 2) in patients with advanced or metastatic solid tumors. Each module contains dose-escalation (Part A) and dose-expansion (Part B).
Interventions
DRUGAZD5863
T cell-engaging bi-specific antibody that targets CLDN18.2 (Claudin18.2) on tumor cells and CD3 on T cells
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study consists of individual modules each evaluating the safety and tolerability of AZD5863 dosed as monotherapy: * Module 1: AZD5863 intravenous administration * Module 2: AZD5863 subcutaneous administration Modules 1 and 2 each consist of two parts: Part A, Dose Escalation and Part B, Dose Expansion.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age ≥ 18 at the time of signing the informed consent * Histologically confirmed diagnosis of adenocarcinoma of the stomach, gastro-esophageal junction, esophagus, or pancreas * Must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Must show positive CLDN18.2 expression in tumor cells as determined by central immunohistochemistry (IHC) * 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 * Must have received at least one prior line of systemic therapy in the advanced/metastatic setting Key
Exclusion criteria
* Unresolved toxicity from prior anticancer therapy of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 except for those defined by the protocol * Participant 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 * 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), active hepatitis B/C, uncontrolled infection with EBV, uncontrolled active systemic fungal, bacterial or other infection * 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 * Participant requires chronic immunosuppressive therapy * Participants on anticoagulation therapy with long-acting anticoagulants or other class of anticoagulants at therapeutic doses
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The number of patients with adverse events | From first dose of study drug up to 90 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 adverse events of special interest | From first dose of study drug up to 90 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 first dose of study drug until the end of Cycle 1 | 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. |
| The number of patients with serious adverse events | From first dose of study drug up to 90 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 |
| Objective Response Rate (ORR) | From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From the start of study treatment/date of randomization to death (to be followed-up for approx. 2 years) | The time from the start of study treatment/date of randomization until death due to any cause. |
| Pharmacokinetics of AZD5863: Area Under the concentration-time curve (AUC) | From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years) | Area under the plasma concentration-time curve |
| Pharmacokinetics of AZD5863: Clearance | From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years) | A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time. |
| Pharmacokinetics of AZD5863: Terminal elimination half-life (t 1/2) | From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years) | Terminal elimination half life. |
| Immunogenicity of AZD5863 | From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years) | The number and percentage of participants who develop anti-drug antibodies (ADAs) measured in serum |
| Pharmacokinetics of AZD5863: Maximum plasma concentration of the study drug (Cmax) | From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years) | Maximum observed plasma concentration of the study drug |
| Preliminary antitumor activity with target expression pre- and post-delivery of AZD5863 | From time of Informed consent, at predefined intervals (including screening, on-treatment or end of treatment) throughout the study (over approx. 2 years) | Measure CLDN18.2 expression (IHC) in baseline and/or on-treatment tumor biopsies and correlate with clinical outcome |
| Objective Response Rate (ORR) | From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 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. |
| Disease Control Rate (DCR) | From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years) | Percentage of patients with confirmed complete or partial response or having stable disease maintained for \>= 11 weeks from first dose, according to response criteria in solid tumours (RECIST 1.1). |
| Duration of response (DoR) | From the first documented response to progressive disease or death in the absence of disease progression (approx. 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). |
| Progression free Survival (PFS) | From the start of study treatment/date of randomization to progressive disease or death in the absence of disease progression (approx. 2 years) | The time from the start of study treatment/date of randomization until RECIST 1.1 defined disease progression or death in the absence of disease progression. |
Countries
China, France, Japan, Netherlands, South Korea, Taiwan, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed