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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
研究概览
简要总结
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.
详细描述
Approximately 110 participants will be assigned to SHR-1210 + capecitabine + oxaliplatin combination therapy (Cohort 1), or SHR-1210 + apatinib combination therapy (Cohort 2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Life expectancy ≥ 12 weeks.
- •Eastern Cooperative Group (ECOG) performance status of 0 to
- •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.
排除标准
- •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.
研究组 & 干预措施
Cohort 1
Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus capecitabine 1000 mg/m^2 twice daily (BID) by continuous oral administration 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 if there is no PD.
干预措施: SHR-1210 (Biological)
Cohort 1
Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus capecitabine 1000 mg/m^2 twice daily (BID) by continuous oral administration 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 if there is no PD.
干预措施: Capecitabine (Drug)
Cohort 1
Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus capecitabine 1000 mg/m^2 twice daily (BID) by continuous oral administration 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 if there is no PD.
干预措施: Oxaliplatin (Drug)
Cohort 1
Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus capecitabine 1000 mg/m^2 twice daily (BID) by continuous oral administration 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 if there is no PD.
干预措施: Apatinib (Drug)
Cohort 2
Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus apatinib 375 mg daily (QD) continuous oral administration of each 3-week cycle.
干预措施: SHR-1210 (Biological)
Cohort 2
Participants receive SHR-1210 200 mg, intravenously (IV) every 3 weeks(Q3W) plus apatinib 375 mg daily (QD) continuous oral administration of each 3-week cycle.
干预措施: Apatinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
时间窗: Up to approximately 6 months.
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.
次要结局
- Duration of Response (DOR) Per RECIST 1.1(Up to 24 months.)
- Number of Subjects With Treatment-related Adverse Events (AEs)(Up to 24 months.)
- Progression-free Survival (PFS) Per RECIST 1.1(Up to 24 months.)
- Disease Control Rate (DCR) Per RECIST 1.1(Up to 24 months.)