A Study of SHR-1210 in Combination With Capecitabine + Oxaliplatin or Apatinib in Treatment of Advanced Gastric Cancer

Study Overview
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Brief Summary
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The purpose of this trial is to estimate overall response rate (ORR) of SHR-1210 combined with capecitabine and oxaliplatin or with apatinib as first-line treatment in subjects with locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Detailed Description
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Approximately 110 participants will be assigned to SHR-1210 + capecitabine + oxaliplatin combination therapy (Cohort 1), or SHR-1210 + apatinib combination therapy (Cohort 2).

Official Title
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A Randomized Phase 2 Study to Evaluate Safety and Efficacy of the Combination of SHR-1210 With Capecitabine + Oxaliplatin or Apatinib as First-line Treatment in Patients With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Conditions
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Gastric Cancer, GastroEsophageal Cancer

Intervention / Treatment
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* Biological: 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 metastatic 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 HER2 inhibitor). Subjects with previous adjuvant/neo-adjuvant therapy completed more than 6 months can be enrolled. Has measurable disease per RECIST 1.1 Life expectancy ≥ 12 weeks 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 received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, or a VEGFR inhibitor. Has known active central nervous system metastases. Has received a live vaccine within 4 weeks prior to the first dose of study treatment With any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, 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. 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), or ventricular arrhythmia which need medical intervention. Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents(within 3 months): systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg. Coagulation abnormalities (INR > 1.5 or APTT > 1.5×ULN), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.

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: Cohort 1<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 375 mg PO qd. | Biological: SHR-1210<br>* SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody<br>* Other names: Camrelizumab;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>* 375 mg administered as continuous oral once daily (QD) of each 3-week cycle.<br>|
| Experimental: Cohort 2<br>Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus apatinib 375 mg daily (QD) continous oral. Study treatment will be started on Day 1 of each 3-week cycle. | Biological: SHR-1210<br>* SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody<br>* Other names: Camrelizumab;Drug: Apatinib<br>* 375 mg administered as continuous oral once daily (QD) of each 3-week cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. | Up to approximately 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) per RECIST 1.1 | PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurs first. | Up to 24 months. | 
| Duration of Response (DOR) per RECIST 1.1 | For participants who demonstrate CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters), DOR is defined as the time from first documented evidence of CR or PR until disease progression per RECIST 1.1 based on assessments by blinded independent central review or death due to any cause, whichever occurs first. | Up to 24 months. | 
| Disease Control Rate (DCR) per RECIST 1.1 | DCR is defined as the percentage of participants in the analysis population who have a CR, PR or SD per RECIST 1.1. | Up to 24 months. | 
| Number of Subjects with treatment-related adverse events (AEs) | Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03. | Up to 24 months. | 

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