A Master Protocol of an Open-Label, Multi-Drug, Multi-Center, Phase II Platform Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of Novel Agents or Combinations as Perioperative Treatment in Participants With Locally Advanced Resectable Gastroesophageal Adenocarcinoma (GEMINI-PeriOp GC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 100
- 试验地点
- 71
- 主要终点
- Number of participants with adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
GEMINI-PeriOp GC study will assess the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of novel agents or novel combinations as perioperative treatment in participants with locally advanced resectable gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma who have not received previous treatment for the disease.
详细描述
This Phase II, open-label, multi-drug, multi-center platform study consists of individual sub-studies/cohorts, each allows the assessment of multiple novel agents or novel combinations.
Participants will be assigned across different sub-studies/cohorts, to have sufficient evaluable participants of the confirmed recommended dose by Safety Review Committee (SRC) for study intervention in each corresponding sub-study/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
- •Histologically documented gastric, GEJ, or esophageal adenocarcinoma with resectable disease
- •Participants who are CLDN18.2-positive in Sub-study 1 or HER2-positive in Sub-study 2; no specific requirements for Sub-study 3
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate organ and bone marrow function
- •Body weight > 35 kg
排除标准
- •Participants had any prior anti-cancer treatment or surgery for the current gastric, GEJ, or esophageal cancer.
- •Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment
- •Central nervous system (CNS) pathology
- •Uncontrolled infections
- •Participants with history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, current ILD/pneumonitis, or suspected ILD/pneumonitis
- •History of another primary malignancy
- •Participants with any known or suspicious distant metastasis
- •Uncontrolled hepatitis B and/or chronic or active hepatitis B
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention
研究组 & 干预措施
Sub-study 3: Rilvegostomig plus FLOT chemotherapy
Participants will receive Rilvegostomig plus FLOT chemotherapy as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Rilvegostomig as adjuvant therapy 2.
干预措施: FLOT Chemotherapy (Drug)
Sub-study 1: Cohort 1a - Sonesitatug Vedotin plus Rilvegostomig and 5-FU or Capecitabine
Participants will receive Sonesitatug Vedotin (Dose A) plus Rilvegostomig and 5-FU or Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose A) plus Rilvegostomig as adjuvant therapy 2.
干预措施: 5-Fluorouracil (5-FU) (Drug)
Sub-study 1: Cohort 1b - Sonesitatug Vedotin plus Rilvegostomig and Capecitabine
Participants will receive Sonesitatug vedotin (Dose B) plus Rilvegostomig and Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose B) plus Rilvegostomig as adjuvant therapy 2.
干预措施: Sonesitatug Vedotin (Drug)
Sub-study 1: Cohort 1b - Sonesitatug Vedotin plus Rilvegostomig and Capecitabine
Participants will receive Sonesitatug vedotin (Dose B) plus Rilvegostomig and Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose B) plus Rilvegostomig as adjuvant therapy 2.
干预措施: Capecitabine (Drug)
Sub-study 1: Cohort 1a - Sonesitatug Vedotin plus Rilvegostomig and 5-FU or Capecitabine
Participants will receive Sonesitatug Vedotin (Dose A) plus Rilvegostomig and 5-FU or Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose A) plus Rilvegostomig as adjuvant therapy 2.
干预措施: Rilvegostomig (Drug)
Sub-study 3: Rilvegostomig plus FLOT chemotherapy
Participants will receive Rilvegostomig plus FLOT chemotherapy as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Rilvegostomig as adjuvant therapy 2.
干预措施: Rilvegostomig (Drug)
Sub-study 1: Cohort 1a - Sonesitatug Vedotin plus Rilvegostomig and 5-FU or Capecitabine
Participants will receive Sonesitatug Vedotin (Dose A) plus Rilvegostomig and 5-FU or Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose A) plus Rilvegostomig as adjuvant therapy 2.
干预措施: Capecitabine (Drug)
Sub-study 1: Cohort 1c - Sonesitatug Vedotin plus Rilvegostomig plus 5-FU and calcium folinate
Participants will receive Sonesitatug Vedotin (Dose C) plus Rilvegostomig plus 5-FU and calcium folinate as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose C) plus Rilvegostomig as adjuvant therapy 2.
干预措施: Rilvegostomig (Drug)
Sub-study 1: Cohort 1c - Sonesitatug Vedotin plus Rilvegostomig plus 5-FU and calcium folinate
Participants will receive Sonesitatug Vedotin (Dose C) plus Rilvegostomig plus 5-FU and calcium folinate as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose C) plus Rilvegostomig as adjuvant therapy 2.
干预措施: 5-Fluorouracil (5-FU) (Drug)
Sub-study 2: T-DXd plus Rilvegostomig and 5-FU or Capecitabine
Participants will receive T-DXd plus Rilvegostomig and 5-FU or Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Rilvegostomig as adjuvant therapy 2.
干预措施: Rilvegostomig (Drug)
Sub-study 1: Cohort 1c - Sonesitatug Vedotin plus Rilvegostomig plus 5-FU and calcium folinate
Participants will receive Sonesitatug Vedotin (Dose C) plus Rilvegostomig plus 5-FU and calcium folinate as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose C) plus Rilvegostomig as adjuvant therapy 2.
干预措施: Calcium folinate (Drug)
Sub-study 2: T-DXd plus Rilvegostomig and 5-FU or Capecitabine
Participants will receive T-DXd plus Rilvegostomig and 5-FU or Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Rilvegostomig as adjuvant therapy 2.
干预措施: Capecitabine (Drug)
Sub-study 1: Cohort 1b - Sonesitatug Vedotin plus Rilvegostomig and Capecitabine
Participants will receive Sonesitatug vedotin (Dose B) plus Rilvegostomig and Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose B) plus Rilvegostomig as adjuvant therapy 2.
干预措施: Rilvegostomig (Drug)
Sub-study 2: T-DXd plus Rilvegostomig and 5-FU or Capecitabine
Participants will receive T-DXd plus Rilvegostomig and 5-FU or Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Rilvegostomig as adjuvant therapy 2.
干预措施: 5-Fluorouracil (5-FU) (Drug)
Sub-study 2: T-DXd plus Rilvegostomig and 5-FU or Capecitabine
Participants will receive T-DXd plus Rilvegostomig and 5-FU or Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Rilvegostomig as adjuvant therapy 2.
干预措施: Trastuzumab Deruxtecan (T-DXd) (Drug)
Sub-study 1: Cohort 1a - Sonesitatug Vedotin plus Rilvegostomig and 5-FU or Capecitabine
Participants will receive Sonesitatug Vedotin (Dose A) plus Rilvegostomig and 5-FU or Capecitabine as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose A) plus Rilvegostomig as adjuvant therapy 2.
干预措施: Sonesitatug Vedotin (Drug)
Sub-study 1: Cohort 1c - Sonesitatug Vedotin plus Rilvegostomig plus 5-FU and calcium folinate
Participants will receive Sonesitatug Vedotin (Dose C) plus Rilvegostomig plus 5-FU and calcium folinate as neoadjuvant combination therapy (pre-surgery period) and adjuvant therapy 1 and later will receive Sonesitatug vedotin (Dose C) plus Rilvegostomig as adjuvant therapy 2.
干预措施: Sonesitatug Vedotin (Drug)
结局指标
主要结局
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
时间窗: Until sub-study completion, up to 38 months
To assess the safety and tolerability of perioperative treatment.
Percentage of participants with pathological complete response (pCR)
时间窗: Until sub-study completion, up to 38 months
pCR is defined as no viable cancer cells, including lymph nodes after complete evaluation in the resected gastric, GEJ, or esophageal cancer specimen and all sampled regional lymph nodes following neoadjuvant treatment.
次要结局
- Surgery completion rate(Until sub-study completion, up to 38 months)
- R0 resection (complete resection) rate(Until sub-study completion, up to 38 months)
- Percentage of participants with tumor downstaging(Until sub-study completion, up to 38 months)
- Disease-free survival (DFS)(Until sub-study completion, up to 38 months)
- Serum concentrations of study interventions(Until sub-study completion, up to 38 months)
- Overall survival (OS)(Until sub-study completion, up to 38 months)
- Event-free survival (EFS)(Until sub-study completion, up to 38 months)
- Objective response rate (ORR)(Until sub-study completion, up to 38 months)
- Number of participants with positive anti-drug antibodies (ADA)(Until sub-study completion, up to 38 months)