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
概览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 625
- 试验地点
- 5
- 主要终点
- To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy
概览
简要总结
| This is a Phase III, 3-arm, randomized, open-label, multi-center, global clinical study in which we are comparing sponsor test drug (AZD0901) with Standard care of Chemotherapy when given to Second- or Later-Line Adult Participants with Advanced/Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma with CLAUDIN 18.2 Positivity. |
Approximately 625 participants will be randomized globally out of which 20 patients will be taken from India . The patient will be randomized 1.1.1 ratio.
Recruitment of participants who have progressed on or after only one line of prior treatment
will be capped at approximately 33% of the total randomized participants.
AZD0901/Investigator’s choice of therapy until PD, or any other discontinuation criteria is met. AZD0901 may continue beyond PD if participant continues to show clinical benefit and provides informed consent. During study treatment crossover is not allowed
Randomization will be stratified by geographical region (Japan and South Korea vs Other Asia
vs RoW), prior gastrectomy (yes vs no), and line of therapy (2L vs 3L+).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Inclusion criteria
- •Capable of giving signed informed consent prior to any mandatory study-specific procedures, sampling, and analyses as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF
- •Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics initiative research that supports the Genomic Initiative (see Appendix D 2).Participants not giving consent for optional genomics initiative research will still be eligible for the main study.
- •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.
- •Type of Participant and Disease Characteristics
- •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 defined as tumour cell expression 25 with IHC at any intensity, as determined prospectively by central IHC testing using the investigational Ventana CLDN18.2 (SP455) IHC assay (prototype assay and or validated assay or an alternative central test as required) from archival tumor collected within past 24 months or from a fresh biopsy.
- •For participants who have received prior CLDN18.2 targeting therapies a new biopsy upon progression must be provided for testing to determine CLDN18.2 expression.
- •Participants with unknown CLDN18.2 status or CLDN18.2 tumour cell expression 25 with IHC at any intensity based on the central test result are ineligible for the study.
- •b) Participants must undergo local (or have had) HER2 testing by IHC/ISH
- •Disease progression on or after at least one prior regimen for advanced or metastatic disease, which included a fluoropyrimidine and a platinum, for advanced or metastatic disease.
排除标准
- •Exclusion Criteria Medical Conditions
- •Participants with known HER2 positive status as defined as IHC 3 plus or IHC 2plues ISH Plus (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.
- •Active or prior documented autoimmune or inflammatory disorders that required systemic treatment or assessed by Investigator as not appropriate to participate due to undue risk.
- •The following are exceptions to this criterion: (a) Vitiligo or alopecia.
- •(b) Hypothyroidism (eg, following Hashimoto’s disease) stable on hormone replacement.
- •(c) Psoriasis or eczema not requiring systemic treatment
- •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.
- •The following are exceptions to this criterion: (a) Participants with history of seizures are permitted if no active seizures in last 5 years.
结局指标
主要结局
To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy
时间窗: To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy | by assessment of PFS in all randomized | participants | OS is defined as time from randomization until the date | of death due to any cause. | 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. | The measure of interest is the HR of OS
by assessment of PFS in all randomized
时间窗: To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy | by assessment of PFS in all randomized | participants | OS is defined as time from randomization until the date | of death due to any cause. | 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. | The measure of interest is the HR of OS
participants
时间窗: To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy | by assessment of PFS in all randomized | participants | OS is defined as time from randomization until the date | of death due to any cause. | 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. | The measure of interest is the HR of OS
To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy by assessment of OS for 3L+ participants
时间窗: To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy | by assessment of PFS in all randomized | participants | OS is defined as time from randomization until the date | of death due to any cause. | 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. | The measure of interest is the HR of OS
次要结局
- To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy by assessment of OS in all randomized participants(OS is defined as time from randomization until the date of death due to any cause.)
- To demonstrate the effectiveness of(AZD0901 relative to Investigator’s choice of therapy by assessment of PFS for 3L+ participants)
- To demonstrate the effectiveness of(AZD0901 relative to Investigator’s choice of therapy by assessment of ORR in all randomized participants)
- To demonstrate the effectiveness of(AZD0901 relative to Investigator’s choice of therapy by assessment of ORR for 3L+ participants)
- To demonstrate the effectiveness of(AZD0901 relative to Investigator’s choice of therapy by assessment of DoR in all randomized participants)
- To demonstrate the effectiveness of(AZD0901 relative to Investigator’s choice of therapy by assessment of DoR for 3L+ participants)
- To assess the PK of AZD0901(Serum concentrations of AZD0901, total antibody and MMAE, and PK parameters (such as peak concentration and trough, as data allow))
- To assess the immunogenicity of AZD0901(Presence of ADAs against AZD0901 in serum)
- 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(Incidence of AEs and SAEs)
- To assess the efficacy of AZD0901(according to RECIST 1.1 using Investigator assessments)
- To assess participant reported physical(function in participants treated with)
- To describe participant reported tolerability, including symptomatic AEs and overall side-effect bother, of AZD0901compared to Investigator’s choice of therapy in all randomized participants who have received(at least one dose of study intervention)
研究者
Mr Sandeep AV
AstraZeneca Pharma India Ltd