A Randomized Controlled Phase III Study to Evaluate the Combination of Disitamab Vedotin, Trastuzumab, and Tislelizumab Versus Chemotherapy (CAPOX) Combined With Trastuzumab With or Without Pembrolizumab as First-Line Treatment for Advanced Gastric/Gastroesophageal Junction Adenocarcinoma With HER2-high Expression
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 555
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (assessed by the BIRC)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of Disitamab Vedotin combined with Trastuzumab and Tislelizumab Versus Chemotherapy Combined with Trastuzumab with or without Pembrolizumab as First-Line Treatment for Advanced Gastric/Gastroesophageal Junction Adenocarcinoma with HER2-high Expression.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily consent to participate in the study and sign the informed consent form
- •Expected survival period >12 weeks
- •ECOG Performance Status 0 or 1
- •Histologically confirmed unresectable locally advanced or metastatic --gastric/gastroesophageal junction adenocarcinoma
- •No prior systemic therapy for locally advanced or metastatic gastric cancer; or disease progression or recurrence occurring ≥6 months after completion of neoadjuvant/adjuvant therapy
- •HER2-high expression
- •At least one assessable lesion according to RECIST v1.1 criteria
- •Adequate organ function
- •Female subjects of childbearing potential must have a negative blood pregnancy test within 7 days prior to the first treatment, and agree not to breastfeed or donate ova from the signing of the informed consent form until 6 months after the last treatment. Male subjects must agree not to donate sperm from the signing of the informed consent form until 6 months after the last treatment.
- •Able to understand the study requirements and willing to comply with the study and follow-up procedures
排除标准
- •Presence of central nervous system (CNS) metastasis and/or carcinomatous meningitis
- •Peripheral neuropathy > Grade 1
- •Tumor lesions with a tendency to bleed
- •Severe gastrointestinal dysfunction that may affect drug intake, transport, or absorption
- •Bone metastases with a risk of paraplegia
- •Past or current interstitial lung disease, or severely impaired lung function
- •Other malignancies within 5 years prior to randomization, except for those expected to be cured with treatment
- •Pregnant or breastfeeding women
研究组 & 干预措施
Chemotherapy (CAPOX) Combined with Trastuzumab With or Without Pembrolizumab
Participants will receive CAPOX, Trastuzumab and Trastuzumab. Only subjects whose PD-L1 expression is confirmed as CPS ≥1 by the central laboratory will receive pembrolizumab. Treatment will continue until the occurrence of intolerable toxicity, disease progression (investigator-assessed), initiation of new anti-tumor therapy, loss to follow-up, withdrawal of informed consent, or death (whichever occurs first).
干预措施: Pembrolizumab (Drug)
Disitamab Vedotin Combined with Trastuzumab and Tislelizumab
Participants will receive Disitamab Vedotin, Trastuzumab and Tislelizumab until the occurrence of intolerable toxicity, disease progression (investigator-assessed), initiation of new anti-tumor therapy, loss to follow-up, withdrawal of informed consent, or death (whichever occurs first).
干预措施: Disitamab Vedotin (Drug)
Disitamab Vedotin Combined with Trastuzumab and Tislelizumab
Participants will receive Disitamab Vedotin, Trastuzumab and Tislelizumab until the occurrence of intolerable toxicity, disease progression (investigator-assessed), initiation of new anti-tumor therapy, loss to follow-up, withdrawal of informed consent, or death (whichever occurs first).
干预措施: Tislelizumab (Drug)
Disitamab Vedotin Combined with Trastuzumab and Tislelizumab
Participants will receive Disitamab Vedotin, Trastuzumab and Tislelizumab until the occurrence of intolerable toxicity, disease progression (investigator-assessed), initiation of new anti-tumor therapy, loss to follow-up, withdrawal of informed consent, or death (whichever occurs first).
干预措施: Trastuzumab (Drug)
Chemotherapy (CAPOX) Combined with Trastuzumab With or Without Pembrolizumab
Participants will receive CAPOX, Trastuzumab and Trastuzumab. Only subjects whose PD-L1 expression is confirmed as CPS ≥1 by the central laboratory will receive pembrolizumab. Treatment will continue until the occurrence of intolerable toxicity, disease progression (investigator-assessed), initiation of new anti-tumor therapy, loss to follow-up, withdrawal of informed consent, or death (whichever occurs first).
干预措施: CAPOX (oxaliplatin/capecitabine) (Drug)
Chemotherapy (CAPOX) Combined with Trastuzumab With or Without Pembrolizumab
Participants will receive CAPOX, Trastuzumab and Trastuzumab. Only subjects whose PD-L1 expression is confirmed as CPS ≥1 by the central laboratory will receive pembrolizumab. Treatment will continue until the occurrence of intolerable toxicity, disease progression (investigator-assessed), initiation of new anti-tumor therapy, loss to follow-up, withdrawal of informed consent, or death (whichever occurs first).
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Progression-Free Survival (assessed by the BIRC)
时间窗: 24 months
Progression-free survival (PFS) is defined as the time from the date of randomization to disease progression per RECIST 1.1 as assessed by Blinded Independent Review Committee (BIRC) or death due to any cause, whichever occurs first.
次要结局
- Overall Survival(up to 5 years)
- Disease Control Rate (assessed by the BIRC and investigators)(24 months)
- Duration of Response (assessed by the BIRC and investigators)(24 months)
- Progression-Free Survival (assessed by the investigator)(24 months)
- Patient-Reported Outcomes (EQ-5D-5L)(24 months)
- Objective Response Rate (assessed by the BIRC and investigators)(24 months)
- Patient-Reported Outcomes (EORTCQLQ-STO22)(24 months)
- Patient-Reported Outcomes (EORTC-QLQ-C30)(24 months)
- Adverse Events(24 months)