A Study to Evaluate SHR-1210 in Combination With Capecitabine + Oxaliplatin Sequenced by SHR-1210 + Apatinib as First-line Therapy in Treatment of Advanced Gastric Cancer

Study Overview
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Brief Summary
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This is a randomized, open-label, multi-center, phase III trial to evaluate the efficacy and safety of SHR-1210 plus capecitabine and oxaliplatin sequenced by apatinib with or without SHR-1210 versus capecitabine and oxaliplatin as first-line therapy in patients with locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Official Title
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A Randomized, Multicenter, Open-Label, Phase 3 Study Comparing the Efficacy and Safety of SHR-1210 Plus Capecitabine and Oxaliplatin Sequenced by Apatinib With or Without SHR-1210 Versus Capecitabine and Oxaliplatin in Subjects With Previously Untreated Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Conditions
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Gastric Cancer, GastroEsophageal Cancer

Intervention / Treatment
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* Drug: SHR-1210
* Drug: Capecitabine
* Drug: Oxaliplatin
* Drug: Apatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or mestastatic adenocarcinoma of stomach or the esophagogastric junction (GEJ) Age ≥ 18 years old, male or female NO previous therapy for advanced/metastatic disease of GC/GEJ (including HER-2 inhibitor). Subjects with previous adjuvant/neo-adjuvant therapy completed more than 6 months can be enrolled. Has measurable disease per RECIST 1.1 Eastern Cooperative Group (ECOG) performance status of 0 to 1 Has adequate organ function Females of childbearing potential (FOCBP), who are not surgically sterile or postmenopausal, must conduct pregnancy test (serum or urine) within 7 days before enrollment, and must not be pregnant or breast-feeding women. If the result is negative, she must agree to use adequate contraception during the experiment and 3 months after the last administration of the test drugs. And non-sterilized males who are sexually active must agree to use adequate contraception during the experiment and 3 months after the last administration of the test drugs. Exclusion Criteria: Has known HER2-positive status Has known active central nervous system metastatases Has received a live vaccine within 4 weeks prior to the first dose of study treatment With any acitve autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatititis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, or a VEGFR inhibitor. Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, Congestive heart failure (New York heart association (NYHA) class > 2), orventricular arrhythmia which need medical intervention. Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents: systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg.

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: A<br>Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus capecitabine 1000 mg/m^2 twice daily (BID) by continous oral adminstration for 14 days, followed by a recovery period of 7 days, plus oxaliplatin 130 mg/m^2, IV q3w; for 4-6 cycles followed by SHR-1210 plus apatinib 250 mg PO qd. | Drug: SHR-1210<br>* Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial<br>Drug: Capecitabine<br>* 1000 mg/m^2 administered as continuous oral twice daily (BID) of each 3-week cycle.<br>Drug: Oxaliplatin<br>* 130 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle.<br>Drug: Apatinib<br>* 250 mg administered as continuous oral once daily (QD) of each 3-week cycle.<br>|
| Active Comparator: B<br>Capecitabine 1000 mg/m^2 twice daily (BID) by continous oral adminstration for 14 days, followed by a recovery period of 7 days, plus Oxaliplatin 130 mg/m^2, IV q3w | Drug: Capecitabine<br>* 1000 mg/m^2 administered as continuous oral twice daily (BID) of each 3-week cycle.<br>Drug: Oxaliplatin<br>* 130 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle.<br>|
| Experimental: C<br>Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus capecitabine 1000 mg/m^2 twice daily (BID) by continous oral adminstration for 14 days, followed by a recovery period of 7 days, plus oxaliplatin 130 mg/m^2, IV q3w; for 4-6 cycles followed by SHR-1210 | Drug: SHR-1210<br>* Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial<br>Drug: Capecitabine<br>* 1000 mg/m^2 administered as continuous oral twice daily (BID) of each 3-week cycle.<br>Drug: Oxaliplatin<br>* 130 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) of SHR-1210 in combination with capecitabine + oxaliplatin sequenced by SHR-1210+apatinib versus capecitabine + oxaliplatin in all subjects or programmed cell death ligand 1 (PD-L1) positive participants |  | Up to 36 months after the first participant is randomized | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 |  | Up to approximately 36 months | 
| Progression-free Survival (PFS) per RECIST 1.1 |  | Up to approximately 36 months | 
| Number of Subjects with treatment-related adverse events (AEs) |  | Up to approximately 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD-1, SHR-1210