The purpose of this study is to measure the efficacy and safety of AZD0901 compared to Investigator's choice of therapy as 2L+ treatment for participants with advanced or metastatic gastric or GEJ adenocarcinoma expressing CLDN18.2.
This is a Phase III, multi-center, open-label, sponsor-blinded, randomized, global study to assess the efficacy and safety of AZD0901 compared to Investigator's choice of therapy as the 2L+ treatment for participants with advanced or metastatic gastric or GEJ adenocarcinoma expressing CLDN18.2, and the clinical performance of the investigational IVD. As part of this combined approach, the efficacy analyses from this study will also provide the basis to evaluate the clinical performance of Ventana CLDN18.2 assay as an IVD device for the identification of patients with advanced or metastatic gastric or GEJ adenocarcinoma expressing CLDN18.2 who may benefit from AZD0901.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
572
Progression Free Survival (PFS) in all randomized participants
The analysis will include all randomized participants. All events will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy.
Time frame: From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 3 years).
Overall Survival (OS) for 3L+ participants
The analysis will include all randomized participants who had at least 2 prior lines of systemic therapy. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy.
Time frame: From date of first dose/randomisation until the date of death due to any cause (approximately 3 years).
OS in all randomized participants
The analysis will include all randomized participants. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy.
Time frame: From date of first dose/randomisation until the date of death due to any cause (approximately 3 years).
PFS for 3L+ participants
The analysis will include all randomized participants who had at least 2 prior lines of systemic therapy. All events will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy.
Time frame: From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 3 years).
Objective Response Rate (ORR) in all randomized participants
ORR is defined as the proportion of participants with at least one visit response of confirmed CR or confirmed PR, as determined by BICR per RECIST 1.1.
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Paclitaxel 80 mg/m2 IV on Days 1, 8, and 15, Q4W (for participants with contraindication to ramucirumab only)
Docetaxel 75-100 mg/m2 IV on Day 1, Q3W (for participants with contraindication to ramucirumab only)
Irinotecan 150-180 mg/m2 IV on Days 1 and 15, Q4W
TAS-102 35 mg/m2 up to a maximum of 80 mg orally twice a day on Days 1 to 5 and Days 8 to 12, Q4W (except China)
Apatinib 500-850 mg at Investigator's discretion based on participant's condition and tolerability, orally once daily, Q4W (China only)
Research Site
Birmingham, Alabama, United States
WITHDRAWNResearch Site
Mobile, Alabama, United States
RECRUITINGResearch Site
Tucson, Arizona, United States
RECRUITINGResearch Site
Duarte, California, United States
RECRUITINGResearch Site
Fullerton, California, United States
WITHDRAWNResearch Site
Irvine, California, United States
RECRUITINGResearch Site
Los Angeles, California, United States
RECRUITINGResearch Site
Los Angeles, California, United States
RECRUITINGResearch Site
Newport Beach, California, United States
RECRUITINGResearch Site
Santa Rosa, California, United States
WITHDRAWN...and 176 more locations
Time frame: From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 3 years).
ORR for 3L+ participants
The analysis will include all randomized participants who had at least 2 prior lines of systemic therapy, with measurable disease at baseline
Time frame: From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 3 years).
Duration of Response (DoR) in all randomized participants
The analysis will include all randomized participants with measurable disease at baseline who have a confirmed response. All events after achieving confirmed response will be included, regardless of whether the participant withdraws from therapy, receives another anticancer therapy or clinically progresses prior to RECIST 1.1.
Time frame: From the date of first documented confirmed response until date of documented progression (approximately 3 years).
Serum concentrations of AZD0901, total antibody and MMAE
To characterise the PK of AZD0901 in participants.
Time frame: From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
Status of ADA to AZD0901
To determine the immunogenicity of AZD0901 in participants.
Time frame: From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]. Changes from baseline in vital signs, clinical laboratory results, and ECGs
To assess the safety and tolerability of AZD0901 as compared with Investigator's choice of therapy in all randomized participants who have received at least one dose of study intervention
Time frame: From start through 30 days post treatment completion and follow up for 90 days.
PK parameters (such as peak concentration, as data allow) of AZD0901, total antibody and MMAE
To characterise the PK of AZD0901 in participants.
Time frame: From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
PK parameters (such as trough concentration, as data allow) of AZD0901, total antibody and MMAE
To characterise the PK of AZD0901 in participants.
Time frame: From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
Prevalence and incidence of ADA to AZD0901
To determine the immunogenicity of AZD0901 in participants.
Time frame: From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
Titer of ADA to AZD0901
To determine the immunogenicity of AZD0901 in participants.
Time frame: From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.