A Study of RC48-ADC Combination Therapies as First-line Treatment in Advanced Metastatic Gastric Cancer
Phase 2
Active, not recruiting
- Conditions
- Gastric Cancer
- Interventions
- Drug: RC48-ADC（2.5mg/kg）Drug: Oxaliplatin（130mg/m2 ）Drug: Capecitabine（1000mg/m2）Drug: RC48-ADC（2.0mg/kg）Drug: Capecitabine（750mg/m2）Drug: Oxaliplatin（100mg/m2 ）
- Registration Number
- NCT05980481
- Lead Sponsor
- RemeGen Co., Ltd.
- Brief Summary
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.
- Detailed Description
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+.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 201
Inclusion Criteria
- 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 1.
- 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.
Exclusion Criteria
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RC48-ADC+Toripalimab+CAPOX (HER2-high expression) RC48-ADC（2.5mg/kg） 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). RC48-ADC+Toripalimab+CAPOX (HER2-high expression) Toripalimab 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). RC48-ADC+Toripalimab+CAPOX (HER2-high expression) Oxaliplatin（130mg/m2 ） 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). RC48-ADC+Toripalimab+CAPOX (HER2-high expression) Capecitabine（1000mg/m2） 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). RC48-ADC+Toripalimab+Trastuzumab (HER2-high expression) RC48-ADC（2.5mg/kg） 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). RC48-ADC+Toripalimab+Trastuzumab (HER2-high expression) Trastuzumab 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). RC48-ADC+Toripalimab+Trastuzumab (HER2-high expression) Toripalimab 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). RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression) RC48-ADC（2.5mg/kg） 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). RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression) Toripalimab 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). RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression) Oxaliplatin（130mg/m2 ） 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). RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression) Capecitabine（1000mg/m2） 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). RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression) RC48-ADC（2.0mg/kg） 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). RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression) Capecitabine（750mg/m2） 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). RC48-ADC+Toripalimab+CAPOX (HER2-intermediate/low expression) Oxaliplatin（100mg/m2 ） 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). Toripalimab+Trastuzumab+CAPOX (HER2-high expression) Trastuzumab 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). Toripalimab+Trastuzumab+CAPOX (HER2-high expression) Toripalimab 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). Toripalimab+Trastuzumab+CAPOX (HER2-high expression) Oxaliplatin（130mg/m2 ） 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). Toripalimab+Trastuzumab+CAPOX (HER2-high expression) Capecitabine（1000mg/m2） 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). Toripalimab+CAPOX (HER2- intermediate/low expression) Toripalimab 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). Toripalimab+CAPOX (HER2- intermediate/low expression) Oxaliplatin（130mg/m2 ） 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). Toripalimab+CAPOX (HER2- intermediate/low expression) Capecitabine（1000mg/m2） 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). RC48-ADC + Toripalimab + Trastuzumab + Capecitabine (HER2-high expression) RC48-ADC（2.5mg/kg） 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). RC48-ADC + Toripalimab + Trastuzumab + Capecitabine (HER2-high expression) Trastuzumab 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). RC48-ADC + Toripalimab + Trastuzumab + Capecitabine (HER2-high expression) Toripalimab 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). RC48-ADC + Toripalimab + Trastuzumab + Capecitabine (HER2-high expression) Capecitabine（1000mg/m2） 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). RC48-ADC+Toripalimab+CAPOX (HER2-negative) RC48-ADC（2.5mg/kg） 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). RC48-ADC+Toripalimab+CAPOX (HER2-negative) Toripalimab 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). RC48-ADC+Toripalimab+CAPOX (HER2-negative) RC48-ADC（2.0mg/kg） 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). RC48-ADC+Toripalimab+CAPOX (HER2-negative) Capecitabine（750mg/m2） 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). RC48-ADC+Toripalimab+CAPOX (HER2-negative) Oxaliplatin（100mg/m2 ） 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). Toripalimab+CAPOX (HER2- negative) Toripalimab 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). Toripalimab+CAPOX (HER2- negative) Oxaliplatin（130mg/m2 ） 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). Toripalimab+CAPOX (HER2- negative) Capecitabine（1000mg/m2） 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).
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) 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).
- Secondary Outcome Measures
Name Time Method Duration of response (DOR) Up to approximately 2 years DOR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death
Safety(adverse event) Up to approximately 2 years to evaluate safety including adverse event rate and adverse event grade.
Progression-free survival (PFS), evaluated by the investigator Up to approximately 2 years Progression-free survival (PFS) refers to the time from the date of randomization to the first researcher's evaluation of disease progression or death (calculated by the event that occurred first). The disease progression will be evaluated by the researchers according to the RECIST 1.1 standard.
Overall survival (OS) Up to approximately 2 years Overall survival (OS) refers to the time from the date of randomization to the date of death of the subject.
Disease Control Rate(DCR) Up to approximately 2 years DCR is the proportion of subjects with optimal overall response to achieve objective remission or stable disease over the course of the study
Trial Locations
- Locations (1)
Beijing Cancer Hospital
🇨🇳Beijing, China
Beijing Cancer Hospital🇨🇳Beijing, ChinaLin Shen, PhDContact010-53806898linshenpku@163.com