AZD0901 Compared With Investigator's Choice of Therapy in Participants With Second- or Later-line Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2
- Conditions
- Gastric CancerGastroesophageal Junction Cancer
- Interventions
- Registration Number
- NCT06346392
- Lead Sponsor
- AstraZeneca
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 589
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Capable of giving signed informed consent prior to any study procedure.
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Participant must be at least 18 years or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the ICF.
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Histologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of gastric, GEJ, or distal esophagus (distal third of the esophagus) and the following requirement:
(a) Participants with positive CLDN18.2 expression from archival tumor collected within past 24 months or from a fresh biopsy.
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Disease progression on or after at least one prior line of treatment (LoT) for advanced or metastatic disease, which included a fluoropyrimidine and a platinum, for advanced or metastatic disease.
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Must have at least one measurable or evaluable lesion assessed by the Investigator based on RECIST 1.1.
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ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
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Predicted life expectancy of ≥ 12 weeks.
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Adequate organ and bone marrow function
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Body weight of ≥ 35 kg.
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Sex and Contraceptive Requirements
- Participants with known HER2 positive status as defined as IHC 3+ or IHC 2+/ISH + (Cases with HER2: CEP17 ratio ≥ 2 or an average HER2 copy number ≥ 6.0 signals/cell are considered positive by ISH). Participants must undergo local (or have had) HER2 testing by IHC/ISH, and the most recent result of HER2 status will be used to determine the eligibility.
- Participant has significant or unstable gastric bleeding and/or untreated gastric ulcers.
- CNS metastases or CNS pathology including: epilepsy, seizures, aphasia, or stroke within 3 months prior to consent, severe brain injury, dementia, Parkinson's disease, neurodegenerative diseases, cerebellar disease, severe uncontrolled mental illness, psychosis, CNS involvement of autoimmune diseases.
- Participant has known clinically significant corneal disease (eg, active keratitis or corneal ulcerations).
- Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss).
- Prior exposure to any ADC with MMAE payload or any CLDN18.2 targeting treatment other than naked monoclonal antibody (eg, CLDN18.2 targeting CAR-T cell therapy, multi-specific antibody including targeting CLDN18.2, etc).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AZD0901 arm 1 AZD0901 Participants in the AZD0901 arm 1 will receive AZD0901 dose level 1 intravenous infusion treatment. Investigator's choice arm Paclitaxel Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies. Investigator's choice arm Apatinib Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies. Investigator's choice arm Ramucirumab+ paclitaxel Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies. AZD0901 Arm 2 AZD0901 Participants in the AZD0901 arm 2 will receive AZD0901 dose level 2 intravenous infusion treatment. Investigator's choice arm Irinotecan Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies. Investigator's choice arm Docetaxel Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies. Investigator's choice arm TAS-102 Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) for 3L+ participants From date of first dose/randomisation until the date of death due to any cause (approximately 3 years). 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.
Progression Free Survival (PFS) in all randomized participants From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 3 years). 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.
- Secondary Outcome Measures
Name Time Method OS in all randomized participants From date of first dose/randomisation until the date of death due to any cause (approximately 3 years). 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.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]. Changes from baseline in vital signs, clinical laboratory results, and ECGs From start through 30 days post treatment completion and follow up for 90 days. 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
PK parameters (such as trough concentration, as data allow) of AZD0901, total antibody and MMAE From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation. To characterise the PK of AZD0901 in participants.
PFS for 3L+ participants From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 3 years). 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.
Status of ADA to AZD0901 From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation. To determine the immunogenicity of AZD0901 in participants.
PK parameters (such as peak concentration, as data allow) of AZD0901, total antibody and MMAE From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation. To characterise the PK of AZD0901 in participants.
Objective Response Rate (ORR) in all randomized participants From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 3 years). 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.
ORR for 3L+ participants From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 3 years). The analysis will include all randomized participants who had at least 2 prior lines of systemic therapy, with measurable disease at baseline
Duration of Response (DoR) in all randomized participants From the date of first documented confirmed response until date of documented progression (approximately 3 years). 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.
Serum concentrations of AZD0901, total antibody and MMAE From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation. To characterise the PK of AZD0901 in participants.
Prevalence and incidence of ADA to AZD0901 From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation. To determine the immunogenicity of AZD0901 in participants.
Titer of ADA to AZD0901 From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation. To determine the immunogenicity of AZD0901 in participants.
Trial Locations
- Locations (1)
Research Site
🇻🇳Vinh, Vietnam