A Study of RC48-ADC Combine With Toripalimab and Chemotherapy or RC48-ADC Combine With Toripalimab and Trastuzumab as First-line Treatment in Local Advanced or Metastatic Gastric Cancer With the HER2 Expression or Non-expression
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 201
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
This is a Phase II/III, randomized, multicenter, open-label clinical trial designed to evaluate safety and efficacy of RC48-ADC combine with Toripalimab and chemotherapy or RC48-ADC combine with Toripalimab and Trastuzumab as first-line treatment in human epidermal growth factor receptor 2 (HER2)-expression or non-expression participants with locally advanced or metastatic gastric cancer.
详细描述
This is a Phase II/III, randomized, multicenter, open-label clinical trial designed to evaluate safety and efficacy of RC48-ADC combine with Toripalimab and chemotherapy or RC48-ADC combine with Toripalimab and Trastuzumab as first-line treatment in human epidermal growth factor receptor 2 (HER2)-expression participants with locally advanced or metastatic gastric cancer. The HER2-expression is defined as: the HER2 IHC 3+ or 2+, or 1+.
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
- •Voluntary agreement to provide written informed consent.
- •Age:18-75 years（including 18 and 75）.
- •Predicted survival ≥ 12 weeks.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
- •Adequate organ function.
- •All subjects must have inoperable, advanced or metastatic gastric or or gastroesophageal adenocarcinoma.
- •Subject must be previously untreated with systemic treatment; Subject that received neoadjuvant chemotherapy with recurrence >6 months from completion of therapy are permitted;
- •HER2-expressing status determined by laboratory to be IHC 1+, 2+ or 3+ or IHC0.
排除标准
- •Active central nervous system (CNS) metastases.
- •Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
- •History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, thyroid cancer ,etal.
- •Known hypersensitivity to antibody-drug conjugate(ADC) or PD-(L)1 or any of its components.
- •Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
研究组 & 干预措施
RC48-ADC+Toripalimab+CAPOX (HER2-high expression)
Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: RC48-ADC（2.5mg/kg） (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-high expression)
Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Toripalimab (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-high expression)
Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Oxaliplatin（130mg/m2 ） (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-high expression)
Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Capecitabine（1000mg/m2） (Drug)
RC48-ADC+Toripalimab+Trastuzumab (HER2-high expression)
Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and Trastuzumab every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: RC48-ADC（2.5mg/kg） (Drug)
RC48-ADC+Toripalimab+Trastuzumab (HER2-high expression)
Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and Trastuzumab every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Trastuzumab (Drug)
RC48-ADC+Toripalimab+Trastuzumab (HER2-high expression)
Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and Trastuzumab every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Toripalimab (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression)
Participants with HER2-intermediate/low expression (IHC 2+/FISH- or IHC 1+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: RC48-ADC（2.5mg/kg） (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression)
Participants with HER2-intermediate/low expression (IHC 2+/FISH- or IHC 1+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Toripalimab (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression)
Participants with HER2-intermediate/low expression (IHC 2+/FISH- or IHC 1+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Oxaliplatin（130mg/m2 ） (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression)
Participants with HER2-intermediate/low expression (IHC 2+/FISH- or IHC 1+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Capecitabine（1000mg/m2） (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression)
Participants with HER2-intermediate/low expression (IHC 2+/FISH- or IHC 1+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: RC48-ADC（2.0mg/kg） (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression)
Participants with HER2-intermediate/low expression (IHC 2+/FISH- or IHC 1+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Capecitabine（750mg/m2） (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression)
Participants with HER2-intermediate/low expression (IHC 2+/FISH- or IHC 1+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Oxaliplatin（100mg/m2 ） (Drug)
Toripalimab+Trastuzumab+CAPOX (HER2-high expression)
Participants with HER2-high expression (IHC2+FISH+ or IHC3+) will receive of Toripalimab every 2 weeks (Q2W) , Trastuzumab every 3 weeks (Q3W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Trastuzumab (Drug)
Toripalimab+Trastuzumab+CAPOX (HER2-high expression)
Participants with HER2-high expression (IHC2+FISH+ or IHC3+) will receive of Toripalimab every 2 weeks (Q2W) , Trastuzumab every 3 weeks (Q3W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Toripalimab (Drug)
Toripalimab+Trastuzumab+CAPOX (HER2-high expression)
Participants with HER2-high expression (IHC2+FISH+ or IHC3+) will receive of Toripalimab every 2 weeks (Q2W) , Trastuzumab every 3 weeks (Q3W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Oxaliplatin（130mg/m2 ） (Drug)
Toripalimab+Trastuzumab+CAPOX (HER2-high expression)
Participants with HER2-high expression (IHC2+FISH+ or IHC3+) will receive of Toripalimab every 2 weeks (Q2W) , Trastuzumab every 3 weeks (Q3W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Capecitabine（1000mg/m2） (Drug)
Toripalimab+CAPOX (HER2- intermediate/low expression)
Participants with HER2- intermediate/low expression (IHC 2+/FISH- or IHC 1+) will receive of Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Toripalimab (Drug)
Toripalimab+CAPOX (HER2- intermediate/low expression)
Participants with HER2- intermediate/low expression (IHC 2+/FISH- or IHC 1+) will receive of Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Oxaliplatin（130mg/m2 ） (Drug)
Toripalimab+CAPOX (HER2- intermediate/low expression)
Participants with HER2- intermediate/low expression (IHC 2+/FISH- or IHC 1+) will receive of Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Capecitabine（1000mg/m2） (Drug)
RC48-ADC + Toripalimab + Trastuzumab + Capecitabine (HER2-high expression)
Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) , Trastuzumab every 3 weeks (Q3W) and Capecitabine every 3 weeks (Q3W), as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: RC48-ADC（2.5mg/kg） (Drug)
RC48-ADC + Toripalimab + Trastuzumab + Capecitabine (HER2-high expression)
Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) , Trastuzumab every 3 weeks (Q3W) and Capecitabine every 3 weeks (Q3W), as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Trastuzumab (Drug)
RC48-ADC + Toripalimab + Trastuzumab + Capecitabine (HER2-high expression)
Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) , Trastuzumab every 3 weeks (Q3W) and Capecitabine every 3 weeks (Q3W), as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Toripalimab (Drug)
RC48-ADC + Toripalimab + Trastuzumab + Capecitabine (HER2-high expression)
Participants with HER2-high expression(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) , Trastuzumab every 3 weeks (Q3W) and Capecitabine every 3 weeks (Q3W), as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Capecitabine（1000mg/m2） (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-negative)
Participants with HER2-negative (IHC0) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: RC48-ADC（2.5mg/kg） (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-negative)
Participants with HER2-negative (IHC0) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Toripalimab (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-negative)
Participants with HER2-negative (IHC0) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: RC48-ADC（2.0mg/kg） (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-negative)
Participants with HER2-negative (IHC0) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Capecitabine（750mg/m2） (Drug)
RC48-ADC+Toripalimab+CAPOX (HER2-negative)
Participants with HER2-negative (IHC0) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Oxaliplatin（100mg/m2 ） (Drug)
Toripalimab+CAPOX (HER2- negative)
Participants with HER2- negative (IHC 0) will receive of Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Toripalimab (Drug)
Toripalimab+CAPOX (HER2- negative)
Participants with HER2- negative (IHC 0) will receive of Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Oxaliplatin（130mg/m2 ） (Drug)
Toripalimab+CAPOX (HER2- negative)
Participants with HER2- negative (IHC 0) will receive of Toripalimab every 2 weeks (Q2W) and CAPOX every 3 weeks (Q3W) , as one treatment period until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).
干预措施: Capecitabine（1000mg/m2） (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Up to approximately 2 years
The objective response rate will be mainly analyzed by according to the RECIST 1.1 standard tumor evaluation by the investigator will be performed).
次要结局
- Duration of response (DOR)(Up to approximately 2 years)
- Safety(adverse event)(Up to approximately 2 years)
- Progression-free survival (PFS), evaluated by the investigator(Up to approximately 2 years)
- Overall survival (OS)(Up to approximately 2 years)
- Disease Control Rate(DCR)(Up to approximately 2 years)