A Study of RC48-ADC in Local Advanced or Metastatic Gastric Cancer With the HER2-Overexpression

Study Overview
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Brief Summary
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This is a Phase III, randomized, multicenter, open-label clinical trial designed to compare RC48-ADC to physician choice standard treatment in participants with human epidermal growth factor receptor 2 (HER2)-overexpression locally advanced or metastatic gastric cancer.

Detailed Description
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This study is a phase III multi-center, randomized, open-label, parallel control study to evaluate the efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody-Monomethyl auristatin E (MMAE) conjugate for the treatment of HER2-overexpression locally advanced or metastatic gastric cancer. The HER2-overexpression is defined as: the HER2 IHC 3+ or 2+, regardless of FISH status.

Official Title
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Randomized, Controlled, Multicenter Phase III Clinical Study Evaluating the Efficacy and Safety of RC48-ADC for the Treatment of Locally Advanced or Metastatic Gastric Cancer With HER2-overexpression

Conditions
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Gastric Cancer, HER2 Overexpressing Gastric Carcinoma

Intervention / Treatment
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* Drug: RC48-ADC
* Drug: Paclitaxel injection
* Drug: Irinotecan Hydrochloride Injection
* Drug: Apatinib Mesylate Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary agreement to provide written informed consent. Male or female, Age ≥ 18 years. Predicted survival ≥ 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. All female subjects will be considered to be of child-bearing potential unless they are postmenopausal, or have been sterilized surgically.Female subjects of child-bearing potential must agree to use two forms of highly effective contraception. Male subjects and their female partner who are of child-bearing potential must agree to use two forms of highly effective contraception. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol. Adequate organ function. All subjects must have inoperable, advanced or metastatic gastric or or gastroesophageal adenocarcinoma Have had progression or intolerance following receipt of at least two systemic chemotherapy for advanced or metastatic disease. The HER2 IHC test result is IHC 2+ or IHC 3+, the subject's previous test results (confirmed by the investigator) or the research center's test results are acceptable; the subject can provide the Specimen of primary or metastatic tumor for HER2 review/judgment. HER2 classic positive (definition: IHC3+ or IHC2+FISH+) and patients who have previously failed standard treatment According to the RECIST 1.1 standard, there is at least one measurable lesion. Exclusion Criteria: Known hypersensitivity to Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection. History of receiving any anti-cancer drug/biologic treatment within 4 weeks prior to trial treatment. History of major surgery within 4 weeks of planned start of trial treatment. Has received a live virus vaccine within 4 weeks of planned start of trial treatment. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above. 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

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<br>Participants will receive RC48-ADC every 2 weeks (Q2W) 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: Recombinant Humanized anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection;|
| Active Comparator: Physician's Choice<br>Participants will receive physician choosed chemotherapy from the following options: Paclitaxel Injection or Irinotecan Hydrochloride Injection or Apatinib Mesylate Tablets oral. | Drug: Paclitaxel injection<br>* Administered according to label, as one option for Physician's Choice (determined before randomization)<br>* Other names: Taxol;Drug: Irinotecan Hydrochloride Injection<br>* Administered according to label, as one option for Physician's Choice (determined before randomization)<br>* Other names: CAMPTO;Drug: Apatinib Mesylate Tablets<br>* Administered according to label, as one option for Physician's Choice (determined before randomization)<br>* Other names: Aitan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Overall survival (OS) refers to the time from the date of randomization to the date of death of the subject. | within approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | within approximately 3 years | 
| Objective remission rate (ORR) | The objective response rate will be mainly analyzed by the independent efficacy evaluation committee according to the RECIST 1.1 standard tumor evaluation (the evaluation by the investigator will also be performed). | within approximately 3 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 | within approximately 3 years | 
| Disease control rate (DCR) | Disease control rate (DCR) is defined as cases where objective remission (assessed as complete remission or partial remission according to RECIST 1.1 standard) or stable disease during the study. | within approximately 3 years | 
| Tumor progression time (TTP) | Time to disease progression (TTP) refers to the time from the random date to the first disease progression (calculated by the event that occurred first). Disease progression will be evaluated by the investigator according to the RECIST 1.1 standard (investigator and Independent Review Committee(IRC) evaluation). | within approximately 3 years | 

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