A Multicenter, Randomized, Double-Blind, Phase III Clinical Study to Evaluate the Efficacy and Safety of Toripalimab Injection Combined With Postoperative Adjuvant Chemotherapy Versus Placebo Combined With Postoperative Adjuvant Chemotherapy in Patients With Gastric or Esophagogastric Junction Adenocarcinoma After Radical Gastrectomy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 878
- 试验地点
- 72
- 主要终点
- DFS in the PD-L1-positive population evaluated by the BICR
研究概览
简要总结
This multicenter, randomized, double-blind phase III study intends to recruit about 878 patients, including PD-L1 positive 660 patients, who have received radical gastrectomy (R0 resection, D2 or more extended lymphadenectomy) with postoperative pathological stage IIB or III (AJCC Cancer Staging Manual, 8th Edition) gastric or EGJ adenocarcinoma to evaluate the efficacy and safety of JS001 combined with postoperative adjuvant chemotherapy versus placebo combined with postoperative adjuvant chemotherapy.
详细描述
"This is a multicenter, randomized, double-blind phase III study, plans to recruit 878 patients who received radical gastrectomy (R0, D2 or higher lymphadenectomy) with postoperative pathological stage II (T4aN0M0) or III (the 8th Edition American Joint Committee on Cancer [AJCC] Cancer Staging Manual) gastric adenocarcinoma and gastroesophageal junction adenocarcinoma, and the study intends to evaluate the efficacy and safety of JS001 combined with postoperative adjuvant chemotherapy versus placebo combined with postoperative adjuvant chemotherapy.
Patients meeting the inclusion criteria will be 1:1 randomized into JS001-chemotherapy group and placebo-chemotherapy group. The random stratification factors include adjuvant chemotherapeutic regimens (XELOX versus SOX) and tumor anatomical sites (gastric adenocarcinoma versus gastroesophageal junction adenocarcinoma).
The study treatment will be initiated 4-6 weeks after surgery, and the investigator will select XELOX (Oxaliplatin + capecitabine) or SOX (Oxaliplatin + S-1, tegafur, gimeracil and oteracil potassium) as the adjuvant chemotherapeutic regimen given as 3-week cycles for up to 8 cycles based on each patient's condition; JS001/placebo will be given for up to 17 cycles after surgery, until intolerable toxicity, disease recurrence, patient's withdrawal of consent, investigator's judgment that the patient needs to be withdrawn from the study treatment, or death, whichever comes first.
Safety evaluation, including vital signs, ECOG score, physical examination and laboratory examinations, will be performed on a regular basis during the treatment.
This study will end after the main analysis node of DFS and unblinding for analysis are achieved, or 5 years after enrollment of the last patient, whichever comes first. The Sponsor is entitled to terminate the study at any time due to specific reasons (e. g, major safety issues, force majeure, etc.).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75 years.
- •No residual tumor (R0) after D2 or greater lymphadenectomy through laparotomy.
- •According to the definition of the 8th edition of the AJCC Cancer Staging Manual, patients with gastric adenocarcinoma confirmed by histopathology, pathological stage II (T4aN0M0) and stage III, including gastroesophageal junction adenocarcinoma (GEJ) patients.
- •Patients need to provide sufficient formalin-fixed paraffin-embedded (FFPE) neoplasm tissue specimens or sections that are confirmed to be PD-L1 positive (CPS ≥ 1) by lab test at the central laboratory.
- •ECOG performance status 0-
- •No metastasis or recurrence as radiologically confirmed.
- •Patients must have adequate organ function as assessed in the laboratory tests.
- •Patients must provide informed consent for this study, and sign the written informed consent form voluntarily before the initiation of the study, and are willing and able to comply with the scheduled visits, treatment plan, laboratory examinations and other study procedures in the study.
- •Female patients of childbearing age must take a serum pregnancy test within 7 days before randomization with negative results, and agree to adopt reliable and effective contraceptive methods during the study.
排除标准
- •Previous use of non-surgical therapy (e.g., radiotherapy, chemotherapy, hormone therapy) for gastric adenocarcinoma.
- •Having liver, peritoneal or other distant metastasis.
- •Having malignant tumors other than gastric adenocarcinoma within 5 years before randomization.
- •Pevious treatment targeting PD-1 receptor or its ligand PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) receptor;
- •Previous history of serious allergy to monoclonal antibody or other biological preparations.
研究组 & 干预措施
JS001 240mg, Q3W with XELOX regimen or SOX regimen
JS001 240mg, will be intravenously administered once every 3 weeks, until 17 cycles XELOX regimen (oxaliplatin + capecitabine) or SOX regimen (oxaliplatin + S-1), given in one therapeutic cycle of 3 weeks for up to 8 cycles XELOX regimen: Oxaliplatin, 130mg/m2, intravenous drip for over 3 hours, day 1, Q3W; capecitabine, 1000mg/m2, orally, twice per day, from day 1 to day 14, Q3W.
SOX regimen: Oxaliplatin, 130mg/m2, intravenous drip for over 3 hours, day 1, Q3W; S-1 Capsules, 40-60mg, orally, twice per day, from day 1 to day 14, Q3W.
干预措施: JS001/Placebo (Biological)
Placebo combine with chemotherapy
XELOX regimen (oxaliplatin + capecitabine) or SOX regimen (oxaliplatin + S-1), given in one therapeutic cycle of 3 weeks for up to 8 cycles XELOX regimen: Oxaliplatin, 130mg/m2, intravenous drip for over 3 hours, day 1, Q3W; capecitabine, 1000mg/m2, orally, twice per day, from day 1 to day 14, Q3W.
SOX regimen: Oxaliplatin, 130mg/m2, intravenous drip for over 3 hours, day 1, Q3W; S-1 Capsules, 40-60mg, orally, twice per day, from day 1 to day 14, Q3W.
干预措施: JS001/placebo combine with Postoperative Adjuvant Chemotherapy (Biological)
结局指标
主要结局
DFS in the PD-L1-positive population evaluated by the BICR
时间窗: 5 years
To evaluate the disease-free survival (DFS) by the blind independent central review (BICR) for toripalimab combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in PD-L1-positive patients with gastric or GEJ adenocarcinoma after radical gastrectomy.
次要结局
- OS in the PD-L1-positive population(5 years)
- DFS in the PD-L1-positive population evaluated by the investigator(5 years)
- DFS in the ITT population evaluated by the BICR and investigator, respectively(5 years)
- OS in the ITT population(5 years)
- DFS rate at 3 years in the PD-L1-positive population and the ITT population evaluated by the BICR and investigator, respectively(3 years)
- DFS rate at 5 years in the PD-L1-positive population and the ITT population evaluated by the BICR and investigator, respectively(5 years)
- OS rate at 3 years in the PD-L1-positive population and the ITT population(3 years)
- OS rate at 5 years in the PD-L1-positive population and the ITT population(5 years)
- Immunogenicity of toripalimab(Up to the 90 days from last dose of toripalimab)
- Blood trough concentration of toripalimab(Up to the 90 days from last dose of toripalimab)