A Phase III, Multicentre, Randomised Controlled Study of Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in First-Line Claudin18.2-Positive, HER2-Negative, Advanced/Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (CLARITY-Gastric 02)
概览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 2,130
- 试验地点
- 286
- 主要终点
- Progression Free Survival (PFS) (Cohort 1 and Cohort 2)
概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of sonesitatug vedotin in combination with capecitabine with or without rilvegostomig in first-line (1L) Claudin18.2 (CLDN18.2)-positive, human epidermal growth factor receptor 2 (HER2)-negative, gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.
详细描述
The purpose of this Phase III study is to evaluate the efficacy and safety of sonesitatug vedotin in combination with capecitabine with or without rilvegostomig in 1L CLDN18.2-positive, HER2-negative gastric, GEJ, and esophageal adenocarcinoma, and the clinical performance of the investigation in vitro diagnostics (IVDs). The study will include 2 cohorts to provide a treatment option for all participants that are HER2-negative and CLDN18.2-positive. Cohort 1 will evaluate sonesitatug vedotin in combination with rilvegostomig with capecitabine in participants who are CLDN18.2-positive and programmed death-ligand 1 (PD-L1) positive. Cohort 2 will evaluate sonesitatug vedotin in combination with capecitabine in participants who are CLDN18.2-positive and PD-L1 negative or immune checkpoint inhibitor (ICI) ineligible.
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, unless a positive result is observed at an interim analysis and access is required as per protocol-defined procedures
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
- •Capable of giving signed informed consent
- •Participant must be 18 years or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent.
- •Previously untreated histologically documented unresectable, locally advanced, or metastatic gastric, GEJ, or distal esophagus (distal third of the esophagus) adenocarcinoma
- •Positive CLDN18.2 expression, as determined prospectively by central IHC testing
- •Confirmed PD-L1 CPS status by central IHC testing and ICI eligibility per investigator judgement is required to determine cohort eligibility as described below:
- •Cohort 1: PD-L1 positive as determined by central IHC testing and the participant is deemed ICI eligible per investigator judgement.
- •Cohort 2: PD-L1 negative as determined by central IHC testing OR the participant is ICI ineligible
- •ECOG performance status of 0 or 1 with no deterioration to \> 1 over the previous 2 weeks prior to baseline at screening and prior to randomisation.
- •Minimum life expectancy of ≥ 12 weeks.
- •At least one lesion (measurable and/or non-measurable) that can be accurately assessed by the investigator based on RECIST 1.
排除标准
- •Known HER2-positive status
- •Significant or unstable gastric bleeding and/or untreated gastric ulcers.
- •Active or history of autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment or assessed by investigator as not appropriate to participate due to undue risk are excluded.
- •CNS pathology
- •Clinically significant pleural effusions or ascites and/or pleural effusions or ascites that require drainage, peritoneal shunt, or indwelling catheter/drain.
- •Require parenteral nutrition support due to gastric or gastrointestinal obstruction.
- •Peripheral neuropathy, sensory or motor, ≥ CTCAE Grade 2 at screening.
- •Persistent toxicities caused by previous anticancer therapy excluding alopecia, not yet improved to Grade ≤ 1 or baseline.
- •Cardiac abnormalities as outlined in the protocol
- •Uncontrolled diabetes or diabetic neuropathy within 3 months prior to randomisation.
研究组 & 干预措施
Arm A
Sonesitatug vedotin + Rilvegostomig + Capecitabine
干预措施: Sonesitatug vedotin (Drug)
Arm B
Sonesitatug vedotin + Nivolumab + Capecitabine
干预措施: Sonesitatug vedotin (Drug)
Arm D
Sonesitatug vedotin + Capecitabine
干预措施: Sonesitatug vedotin (Drug)
Arm B
Sonesitatug vedotin + Nivolumab + Capecitabine
干预措施: Nivolumab (Drug)
Arm A
Sonesitatug vedotin + Rilvegostomig + Capecitabine
干预措施: Capecitabine (Drug)
Arm A
Sonesitatug vedotin + Rilvegostomig + Capecitabine
干预措施: Rilvegostomig (Drug)
Arm C
Nivolumab + CAPOX OR Nivolumab + FOLFOX
- nivolumab, capecitabine, oxaliplatin
- nivolumab, 5-Fluorouracil, leucovorin, oxaliplatin
干预措施: Capecitabine (Drug)
Arm C
Nivolumab + CAPOX OR Nivolumab + FOLFOX
- nivolumab, capecitabine, oxaliplatin
- nivolumab, 5-Fluorouracil, leucovorin, oxaliplatin
干预措施: Leucovorin (Drug)
Arm D
Sonesitatug vedotin + Capecitabine
干预措施: Capecitabine (Drug)
Arm B
Sonesitatug vedotin + Nivolumab + Capecitabine
干预措施: Capecitabine (Drug)
Arm C
Nivolumab + CAPOX OR Nivolumab + FOLFOX
- nivolumab, capecitabine, oxaliplatin
- nivolumab, 5-Fluorouracil, leucovorin, oxaliplatin
干预措施: Nivolumab (Drug)
Arm C
Nivolumab + CAPOX OR Nivolumab + FOLFOX
- nivolumab, capecitabine, oxaliplatin
- nivolumab, 5-Fluorouracil, leucovorin, oxaliplatin
干预措施: 5-Fluorouracil (Drug)
Arm C
Nivolumab + CAPOX OR Nivolumab + FOLFOX
- nivolumab, capecitabine, oxaliplatin
- nivolumab, 5-Fluorouracil, leucovorin, oxaliplatin
干预措施: Oxaliplatin (Drug)
Arm E
Zolbetuximab + CAPOX or Zolbetuximab + FOLFOX:
- zolbetuximab, capecitabine, oxaliplatin
- zolbetuximab, 5-Fluorouracil, leucovorin, oxaliplatin
CAPOX or FOLFOX:
- oxaliplatin, capecitabine,
- 5-Fluorouracil, leucovorin, oxaliplatin
干预措施: Capecitabine (Drug)
Arm E
Zolbetuximab + CAPOX or Zolbetuximab + FOLFOX:
- zolbetuximab, capecitabine, oxaliplatin
- zolbetuximab, 5-Fluorouracil, leucovorin, oxaliplatin
CAPOX or FOLFOX:
- oxaliplatin, capecitabine,
- 5-Fluorouracil, leucovorin, oxaliplatin
干预措施: Leucovorin (Drug)
Arm E
Zolbetuximab + CAPOX or Zolbetuximab + FOLFOX:
- zolbetuximab, capecitabine, oxaliplatin
- zolbetuximab, 5-Fluorouracil, leucovorin, oxaliplatin
CAPOX or FOLFOX:
- oxaliplatin, capecitabine,
- 5-Fluorouracil, leucovorin, oxaliplatin
干预措施: Zolbetuximab (Drug)
Arm E
Zolbetuximab + CAPOX or Zolbetuximab + FOLFOX:
- zolbetuximab, capecitabine, oxaliplatin
- zolbetuximab, 5-Fluorouracil, leucovorin, oxaliplatin
CAPOX or FOLFOX:
- oxaliplatin, capecitabine,
- 5-Fluorouracil, leucovorin, oxaliplatin
干预措施: Oxaliplatin (Drug)
Arm E
Zolbetuximab + CAPOX or Zolbetuximab + FOLFOX:
- zolbetuximab, capecitabine, oxaliplatin
- zolbetuximab, 5-Fluorouracil, leucovorin, oxaliplatin
CAPOX or FOLFOX:
- oxaliplatin, capecitabine,
- 5-Fluorouracil, leucovorin, oxaliplatin
干预措施: 5-Fluorouracil (Drug)
结局指标
主要结局
Progression Free Survival (PFS) (Cohort 1 and Cohort 2)
时间窗: Up to approximately 5 years
PFS is defined as time from randomisation until progression per RECIST 1.1, or death due to any cause, whichever occurs first.
Overall Survival (OS) (Cohort 1)
时间窗: Up to approximately 5 years
OS is defined as the time from randomisation until the date of death due to any cause.
次要结局
- Overall Survival (OS) (Cohort 2)(Up to approximately 5 years)
- Overall Survival (OS) (Cohort 1)(Up to approximately 5 years)
- Progression Free Survival (PFS) (Cohort 1)(Up to approximately 5 years)
- Objective Response Rate (ORR) (Cohort 1 and Cohort 2)(Up to approximately 5 years)
- Duration of Response (DoR) (Cohort 1 and Cohort 2)(Up to approximately 5 years)
- Pharmacokinetics of sonesitatug vedotin (Cohort 1 and Cohort 2)(Up to approximately 5 years)
- Immunogenicity of sonesitatug vedotin (Cohort 1 and Cohort 2)(Up to approximately 5 years)
- Pharmacokinetics of rilvegostomig (Cohort 1)(Up to approximately 5 years)
- Immunogenicity of rilvegostomig (Cohort 1)(Up to approximately 5 years)
- Safety and tolerability (Cohort 1 and Cohort 2)(Up to approximately 5 years)