A Randomized, Multicenter, Phase 3 Study of Zanidatamab in Combination With Chemotherapy With or Without Tislelizumab in Subjects With HER2-positive Unresectable Locally Advanced or Metastatic Gastroesophageal Adenocarcinoma (GEA)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 920
- 试验地点
- 421
- 主要终点
- Progression-free survival (PFS) by BICR
研究概览
简要总结
This study is being done to find out if zanidatamab, when given with chemotherapy plus or minus tislelizumab, is safe and works better than trastuzumab given with chemotherapy.
The patients in this study will have advanced human epidermal growth factor 2 (HER2)-positive stomach and esophageal cancers that are no longer treatable with surgery (unresectable) or chemoradiation, and/or have grown or spread to other parts of the body (metastatic).
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
- 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 confirmed unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISH positivity per central assessment. Subjects with esophageal adenocarcinoma must not be eligible for combined chemoradiotherapy at the time of enrollment
- •Assessable (measurable or non-measurable) disease as defined by RECIST 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, assessed within 3 days prior to randomization
- •Adequate organ function
- •Left ventricular ejection fraction (LVEF) ≥ 50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA)
排除标准
- •Prior treatment with a HER2-targeted agent, with the exception of subjects who received HER2-targeted treatment for breast cancer > 5 years prior to initial diagnosis of GEA
- •Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- •Prior treatment with systemic antineoplastic therapy or intraperitoneal chemotherapy for unresectable locally advanced, recurrent or metastatic GEA
- •Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks prior to randomization. Stable, treated brain metastases are allowed (defined as subjects who are completely off steroids and anticonvulsants and are neurologically stable with no evidence of radiographic progression for at least 4 weeks prior to randomization)
- •Known history of or ongoing leptomeningeal disease (LMD)
- •Known additional malignancy that is not considered cured or that has required treatment within the past 3 years
- •Known active hepatitis
- •Any history of human immunodeficiency virus (HIV) infection
- •Known SARS-CoV-2 infection; subjects with prior infection that has resolved per local institutions' requirements and screening guidance are eligible
- •QTc Fridericia (QTcF) > 470 ms
- •Clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic congestive heart failure (CHF)
研究组 & 干预措施
Arm A
Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP)
干预措施: Trastuzumab (Drug)
Arm A
Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP)
干预措施: Capecitabine (Drug)
Arm B
Zanidatamab plus physician's choice of CAPOX or FP
干预措施: Zanidatamab (Drug)
Arm B
Zanidatamab plus physician's choice of CAPOX or FP
干预措施: Capecitabine (Drug)
Arm B
Zanidatamab plus physician's choice of CAPOX or FP
干预措施: Cisplatin (Drug)
Arm C
Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP
干预措施: Tislelizumab (Drug)
Arm C
Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP
干预措施: 5-Fluorouracil (Drug)
Arm C
Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP
干预措施: Zanidatamab (Drug)
Arm A
Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP)
干预措施: Cisplatin (Drug)
Arm A
Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP)
干预措施: Oxaliplatin (Drug)
Arm A
Trastuzumab (Herceptin®) plus physician's choice of capecitabine plus oxaliplatin (CAPOX) or 5-fluorouracil (5-FU) plus cisplatin (FP)
干预措施: 5-Fluorouracil (Drug)
Arm B
Zanidatamab plus physician's choice of CAPOX or FP
干预措施: 5-Fluorouracil (Drug)
Arm C
Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP
干预措施: Capecitabine (Drug)
Arm C
Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP
干预措施: Cisplatin (Drug)
Arm B
Zanidatamab plus physician's choice of CAPOX or FP
干预措施: Oxaliplatin (Drug)
Arm C
Zanidatamab and tislelizumab plus physician's choice of CAPOX or FP
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Progression-free survival (PFS) by BICR
时间窗: Up to 2.5 years
The time from randomization to the date of documented disease progression (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1) as assessed by blinded independent central review (BICR) or death from any cause
Overall survival
时间窗: Up to 3.5 years
The time from randomization to death due to any cause
次要结局
- Confirmed objective response rate (ORR) by BICR(Up to 2.5 years)
- Duration of response (DOR) by BICR(Up to 2.5 years)
- PFS per Investigator assessment(Up to 2.5 years)
- Confirmed ORR per Investigator assessment(Up to 2.5 years)
- DOR per Investigator assessment(Up to 2.5 years)
- Assessment of Contribution of Components based on Progression-free Survival (PFS) by BICR(Up to 2.5 years)
- Assessment of Contribution of Components based on Overall Survival(Up to 3.5 years)
- Incidence of adverse events(Up to 2 years)
- Incidence of clinical laboratory abnormalities(Up to 2 years)
- Health-related quality of life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (core cancer questionnaire) C30 (QLQ-C30)(Up to 2.5 years)
- HRQoL as assessed by the EORTC Quality of Life Questionnaire (oesophago-gastric module) OG25 (QLQ-OG25)(Up to 2.5 years)
- HRQoL as assessed by the EuroQol 5-dimensions 5-levels (EQ-5D-5L) questionnaire(Up to 2.5 years)
- Serum concentration of zanidatamab and tislelizumab(Up to 2 years)
- Incidence of anti-drug antibodies (ADAs)(Up to 2 years)