A Phase III Multi-center, Open-label, Sponsor-blinded, Randomized Study of AZD0901 Monotherapy Compared With Investigator's Choice of Therapy in Second- or Later-Line Adult Participants With Advanced/Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2 (CLARITY Gastric 01)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 594
- 试验地点
- 158
- 主要终点
- Overall Survival (OS) for 3L+ participants
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
This is an open-label study; however, it will be conducted 'sponsor-blind' and the specific treatment to be taken by a participant will be assigned using an IRT/RTSM. To maintain the integrity of the study, sponsor access to treatment records will be restricted, and, in particular, under no circumstances will the sponsor undertake any efficacy analysis by treatment arm during the study. A Study Integrity Plan will be generated in which nominated individuals who will be granted access to any treatment-revealing data will be pre-specified, with their reason for requiring access detailed.
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Capable of giving signed informed consent prior to any study procedure.
- •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.
- •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.
- •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.
- •Must have at least one measurable or evaluable lesion assessed by the Investigator based on RECIST 1.
- •ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
- •Predicted life expectancy of ≥ 12 weeks.
- •Adequate organ and bone marrow function
- •Body weight of ≥ 35 kg.
- •Sex and Contraceptive Requirements
排除标准
- •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 or aphasia 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).
- •History of thromboembolic events:
- •Participants with venous thromboembolism within the past 6 months prior to randomization: participants with venous port or catheter thrombosis or superficial venous thrombus that do not require treatment or are stable on treatment with anticoagulants are excepted
- •History of arterial thromboembolism within the past 12 months prior to randomization
- •As judged by the Investigator, any evidence of diseases which in the Investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
研究组 & 干预措施
Investigator's choice arm
Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies.
干预措施: Docetaxel (Drug)
AZD0901 arm 1
Participants in the AZD0901 arm 1 will receive AZD0901 dose level 1 intravenous infusion treatment.
干预措施: AZD0901 (Drug)
Investigator's choice arm
Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies.
干预措施: TAS-102 (Drug)
Investigator's choice arm
Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies.
干预措施: Apatinib (Drug)
AZD0901 Arm 2
Participants in the AZD0901 arm 2 will receive AZD0901 dose level 2 intravenous infusion treatment. (Enrolment was closed)
干预措施: AZD0901 (Drug)
Investigator's choice arm
Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies.
干预措施: Ramucirumab+ paclitaxel (Drug)
Investigator's choice arm
Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies.
干预措施: Paclitaxel (Drug)
Investigator's choice arm
Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies.
干预措施: Irinotecan (Drug)
结局指标
主要结局
Overall Survival (OS) for 3L+ participants
时间窗: 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
时间窗: 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.
次要结局
- OS in all randomized participants(From date of first dose/randomisation until the date of death due to any cause (approximately 3 years).)
- 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.)
- 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.)
- Duration of Response (DoR) in all randomized participants(From the date of first documented confirmed response until date of documented progression (approximately 3 years).)
- PFS for 3L+ participants(From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 3 years).)
- Status of ADA to AZD0901(From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.)
- 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.)
- 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 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).)
- Serum concentrations of AZD0901, total antibody and MMAE(From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.)
- Prevalence and incidence of ADA to AZD0901(From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.)
- Titer of ADA to AZD0901(From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.)