A Trial of SHR1701 Plus Chemotherapy in Patients With Gastric or Gastroesophageal Cancer

Study Overview
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Brief Summary
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This study is a randomized, Double-Blind, multi-center Phase III clinical study, aimed to evaluate the efficacy and safety of SHR1701 combined with chemotherapy in the treatment of Previously Untreated, Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer. For Part 1 study，the tolerability of SHR-1701 will be evaluated and determine the recommended dose for Part 2.For Part 2 study, all enrolled patients will be randomized to 2 groups and continuously treated until the end criteria of treatment was met.

Official Title
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A Randomized, Double-Blind, Multi-Center, Phase III Clinical Study of SHR-1701 Plus Chemotherapy Versus Placebo Plus Chemotherapy as Treatment in Patients With Previously Untreated, Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Conditions
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Gastric or Gastroesophageal Junction Cancer

Intervention / Treatment
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* Drug: SHR-1701、CAPOX
* Drug: Placebo、CAPOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed diagnosis of locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ)adenocarcinoma. HER2 overexpression or amplification negative. Female or male, 18 years of age or above. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1. Patients who are willing and able to provide the signed informed consent form, willing and able to comply with all the scheduled visits, study treatment, laboratory tests, and other study procedures. Exclusion Criteria: Squamous cell carcinoma, undifferentiated carcinoma, or other histological types of gastric cancer. Presence of inadequately treated CNS metastases, or uncontrolled or symptomatic active CNS metastases ，leptomeningeal disease, and/or rapid progression. Presence of uncontrolled pleural effusion or ascites despite puncture drainage within 14 days prior to randomization. More than 20% weight loss within 2 months prior to randomization. Diagnosed with other malignant tumors within 5 years prior to enrollment. Presence of any active, known or suspected autoimmune disease. Prior treatment with TGF-β inhibitor, anti-PD-1/PD-L1 antibodies, anti-PD-L2 antibodies, anti-CD137 antibodies, anti-CTLA-4 antibodies, or other drugs/antibodies. Severe, unhealed, or dehisced wounds and active ulcers or untreated fractures.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group A<br> | Drug: SHR-1701、CAPOX<br>* SHR-1701 with CAPOX (CAPOX:Oxaliplatin,Capecitabine)<br>|
| Placebo Comparator: Treatment group B<br> | Drug: Placebo、CAPOX<br>* Placebo with CAPOX (CAPOX:Oxaliplatin,Capecitabine)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs and SAEs in part 1 study | The number and proportion of subjects with dose limiting toxicity.The safety endpoints, including incidence and severity of adverse events (AEs) and serious adverse events (SAEs) . | up to 2 years | 
| PFS in part 2 study assessed based on BICR | Progression-free survival(PFS) assessed based on BICR per RECIST 1.1 | up to 2 years | 
| OS in part 2 study | Overall survival (OS) | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR in part 1 study | Objective response rate (ORR) as assessed by the investigator per RECIST 1.1 | up to 2 years | 
| PFS in part 1 study | Progression free survival (PFS); as assessed by the investigator per RECIST 1.1 | up to 2 years | 
| DoR in part 1 study | Duration of response (DoR) as assessed by the investigator per RECIST 1.1 | up to 2 years | 
| OS in part 1 study | Overall survival (OS) | up to 3 years | 
| ORR in part 2 study | ORR in subjects with PD-L1 positive and all subjects assessed by BICR per RECIST 1.1 | up to 2 years | 
| PFS in part 2 study assessed by investigator | PFS in subjects with PD-L1 positive and all subjects assessed by investigator as per RECIST 1.1 | up to 2 years | 
| AEs and SAEs in part 2 study | Safety endpoints, including incidence and severity of AEs and SAEs as per NCI-CTCAE v5.0 criteria. | up to 2 years | 
| EORTC QLQ-C30 score |  | up to 2 years | 
| EORTC QLQ-STO22 score |  | up to 2 years | 
| EQ-5D-5L score |  | up to 2 years | 
| DoR in part 2 study | DoR in subjects with PD-L1 positive and all subjects assessed by BICR per RECIST 1.1 | up to 2 years |