An Open-Label, Multi-Drug, Multi-Centre, Phase II Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 163
- 试验地点
- 45
- 主要终点
- ORR (per RECIST 1.1 as assessed by Investigator)
研究概览
简要总结
This is a Phase II, open-label, multi-drug, multi-centre study designed to assess the efficacy, safety, tolerability, pharmacokinetics, and immunogenicity of novel combination therapies in participants with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.
详细描述
Approximately 360 participants will be assigned across 4 substudies, with approximately 60 evaluable participants of the confirmed recommend dose by SRC for study intervention in each corresponding substudy/cohort.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years or older at the time of signing the ICF.
- •Body weight > 35 kg.
- •Previously untreated for unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
- •Has measurable target disease assessed by the Investigator based on RECIST 1.
- •ECOG PS zero or one.
- •Life expectancy of at least 12 weeks.
- •Adequate organ and bone marrow function.
- •Has central lab confirmed Claudin18.2 status at screening from archival tumour collected within past 24 months or from a fresh biopsy when Substudy 3, Substudy 4 i s open for recruitment.
排除标准
- •Participants with HER2-positive (3+ by IHC, or 2+ by IHC and positive by in situhybridisation) or indeterminate gastric or GEJ carcinoma.
- •Untreated or progressive CNS metastatic disease, any leptomeningeal disease, or cord compression.
- •Participants with ascites which cannot be controlled with appropriate interventions.
- •Active infectious diseases, including tuberculosis, HIV infection, or hepatitis B/C.
- •Uncontrolled intercurrent illness.
- •Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment.
- •History of another primary malignancy.
- •Previous treatment with an immune-oncology agent.
- •Previous treatment with any modalities of Claudin18.2 target therapy or MMAE exposure (when Substudy 3, Substudy 4 is open for recruitment).
研究组 & 干预措施
Substudy 1
Volrustomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)
干预措施: FOLFOX (Drug)
Substudy 1
Volrustomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)
干预措施: XELOX (Drug)
Substudy 2
Rilvegostomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)
干预措施: XELOX (Drug)
Substudy 3
AZD0901 plus volrustomig and 5-fluorouracil or capecitabine
干预措施: Volrustomig (Drug)
Substudy 3
AZD0901 plus volrustomig and 5-fluorouracil or capecitabine
干预措施: AZD0901 (Drug)
Substudy 3
AZD0901 plus volrustomig and 5-fluorouracil or capecitabine
干预措施: 5-Fluorouracil (Drug)
Substudy 3
AZD0901 plus volrustomig and 5-fluorouracil or capecitabine
干预措施: Capecitabine (Drug)
Substudy 4, Cohort 4a2
Sonesitatug vedotin (AZD0901) plus rilvegostomig and 5-fluorouracil
干预措施: Rilvegostomig (Drug)
Substudy 4, Cohort 4a1
Sonesitatug vedotin (AZD0901) plus rilvegostomig and 5-fluorouracil or capecitabine
干预措施: Rilvegostomig (Drug)
Substudy 4, Cohort 4a1
Sonesitatug vedotin (AZD0901) plus rilvegostomig and 5-fluorouracil or capecitabine
干预措施: AZD0901 (Drug)
Substudy 4, Cohort 4a1
Sonesitatug vedotin (AZD0901) plus rilvegostomig and 5-fluorouracil or capecitabine
干预措施: 5-Fluorouracil (Drug)
Substudy 2
Rilvegostomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)
干预措施: FOLFOX (Drug)
Substudy 4, Cohort 4a1
Sonesitatug vedotin (AZD0901) plus rilvegostomig and 5-fluorouracil or capecitabine
干预措施: Capecitabine (Drug)
Substudy 4, Cohort 4a2
Sonesitatug vedotin (AZD0901) plus rilvegostomig and 5-fluorouracil
干预措施: AZD0901 (Drug)
Substudy 4, Cohort 4a2
Sonesitatug vedotin (AZD0901) plus rilvegostomig and 5-fluorouracil
干预措施: 5-Fluorouracil (Drug)
Substudy 4, Cohort 4b
Sonesitatug vedotin (AZD0901) plus capecitabine
干预措施: AZD0901 (Drug)
Substudy 4, Cohort 4b
Sonesitatug vedotin (AZD0901) plus capecitabine
干预措施: Capecitabine (Drug)
Substudy 2
Rilvegostomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)
干预措施: Rilvegostomig (Drug)
Substudy 1
Volrustomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF)
干预措施: Volrustomig (Drug)
结局指标
主要结局
ORR (per RECIST 1.1 as assessed by Investigator)
时间窗: Through substudy completion, an average of 2 years
the proportion of participants who have a confirmed complete response or confirmed partial response, as determined by the Investigator at local site per RECIST 1.1.
PFS6 (per RECIST 1.1 as assessed by Investigator)
时间窗: Through substudy completion, an average of 2 years
the proportion of participants alive and progression-free at 6 months.
次要结局
- other safety related endpoints(Through substudy completion, an average of 2 years)
- PFS per RECIST 1.1 as assessed by the Investigator(Through substudy completion, an average of 2 years)
- OS(Through substudy completion, an average of 2 years)
- DoR per RECIST 1.1 based on Investigator assessment.(Through substudy completion, an average of 2 years)