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 Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A 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
Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial
Drug: Capecitabine
1000 mg/m^2 administered as continuous oral twice daily (BID) of each 3-week cycle.
Drug: Oxaliplatin
130 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle.
Drug: Apatinib
250 mg administered as continuous oral once daily (QD) of each 3-week cycle.
|
| Active Comparator: B 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
1000 mg/m^2 administered as continuous oral twice daily (BID) of each 3-week cycle.
Drug: Oxaliplatin
130 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle.
|
| Experimental: C 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
Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial
Drug: Capecitabine
1000 mg/m^2 administered as continuous oral twice daily (BID) of each 3-week cycle.
Drug: Oxaliplatin
130 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
Criteria
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.
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Has measurable disease per RECIST 1.1
-
Eastern Cooperative Group (ECOG) performance status of 0 to 1
-
Has adequate organ function
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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:
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Has known HER2-positive status
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Has known active central nervous system metastatases
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Has received a live vaccine within 4 weeks prior to the first dose of study treatment
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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.
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Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, or a VEGFR inhibitor.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Cancer Hospital, Peking University | Beijing | Beijing | China |
Sponsors and Collaborators
- Jiangsu HengRui Medicine Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SHR-1210-III-311