A Study of RC48-ADC Combination Therapies as First-line Treatment in Advanced Metastatic Gastric Cancer

Study Overview
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Brief Summary
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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 Herceptin as first-line treatment in human epidermal growth factor receptor 2 (HER2)-expression participants with locally advanced or metastatic gastric cancer.

Detailed Description
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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 Herceptin 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+.

Official Title
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A Study of RC48-ADC Combine With Toripalimab and Chemotherapy or RC48-ADC Combine With Toripalimab and Herceptin as First-line Treatment in Local Advanced or Metastatic Gastric Cancer With the HER2 Expression

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: RC48-ADC
* Drug: Herceptin
* Drug: Toripalimab
* Drug: Oxaliplatin injection
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary agreement to provide written informed consent. Age:18-70 years（including 18 and 70）. 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+. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RC48-ADC+Toripalimab+CAPOX<br>Participants with HER2 positive(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab 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). | Drug: RC48-ADC<br>* 2.5 mg/kg IV every 2 weeks<br>* Other names: Disitamab Vedotin;Drug: Toripalimab<br>* 3.0 mg/kg IV every 2 weeks<br>* Other names: JS001;Drug: Oxaliplatin injection<br>* 100mg/m2 Q3W<br>* Other names: Oxaliplatin;Drug: Capecitabine<br>* 1000mg/m2 Q3W<br>* Other names: Capecitabine Tablets;|
| Experimental: RC48-ADC+Toripalimab+Herceptin<br>Participants with HER2 positive(IHC2+FISH+ or IHC3+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab 2 weeks (Q2W) and Herceptin 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). | Drug: RC48-ADC<br>* 2.5 mg/kg IV every 2 weeks<br>* Other names: Disitamab Vedotin;Drug: Herceptin<br>* First load dose is 8.0mg , then 6.0 mg/kg IV every 3 weeks<br>* Other names: Trastuzumab;Drug: Toripalimab<br>* 3.0 mg/kg IV every 2 weeks<br>* Other names: JS001;|
| Experimental: RC48-ADC+Toripalimab+CAPOX(HER2-low)<br>Participants with HER2-low (IHC1+) will receive of RC48-ADC every 2 weeks (Q2W), Toripalimab 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). | Drug: RC48-ADC<br>* 2.5 mg/kg IV every 2 weeks<br>* Other names: Disitamab Vedotin;Drug: Toripalimab<br>* 3.0 mg/kg IV every 2 weeks<br>* Other names: JS001;Drug: Oxaliplatin injection<br>* 100mg/m2 Q3W<br>* Other names: Oxaliplatin;Drug: Capecitabine<br>* 1000mg/m2 Q3W<br>* Other names: Capecitabine Tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety(adverse event) | to evaluate safety including adverse event rate and adverse event grade. | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective remission rate (ORR) | The objective response rate will be mainly analyzed by according to the RECIST 1.1 standard tumor evaluation by the investigator will be performed). | Up to approximately 2 years | 
| Progression-free survival (PFS), evaluated by the investigator | 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. | Up to approximately 2 years | 
| Overall survival (OS) | Overall survival (OS) refers to the time from the date of randomization to the date of death of the subject. | Up to approximately 2 years | 
| Duration of relief (DOR) | DOR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death | Up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RC48-ADC, HER2 expression, Gastric cancer