A Phase IIb, Clinical Trial to Study the Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With TS-1+Cisplatin or TS-1+Oxaliplatin as a First Line Chemotherapy in Participants With Advanced or Recurrent Gastric Cancer (KEYNOTE-659)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 25
- 主要终点
- Objective Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR)
研究概览
简要总结
The purpose of this study is to estimate objective response rates (ORRs) of pembrolizumab + oxaliplatin + TS-1 and pembrolizumab + cisplatin + TS-1, as first-line treatment for gastric cancer in programmed death-ligand 1 (PD-L1) positive, human epidermal growth factor receptor 2 (HER2/neu)-negative participants with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.
详细描述
Approximately 45 participants will be assigned to pembrolizumab + oxaliplatin + TS-1 combination therapy (Cohort 1) first, and then 45 participants will be assigned to pembrolizumab + cisplatin + TS-1 combination therapy (Cohort 2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma
- •Has a PD-L1 positive tumor as determined by immunohistochemistry (IHC) at a central laboratory
- •Has measurable disease as defined by RECIST 1.1 as determined by investigator assessment. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
- •Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test at the timing of enrollment
- •Participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
- •Has adequate organ function
排除标准
- •Has squamous cell or undifferentiated gastric cancer
- •HER2-positive status
- •Has had previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer
- •A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation
- •Has received prior therapy with a platinum-based anti-cancer drug
- •Has had major surgery, open biopsy or significant traumatic injury within 28 days prior to enrollment, or anticipation of the need for major surgery during the course of study treatment
- •Has had radiotherapy within 14 days of enrollment
- •Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
- •Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years with use of disease modifying agents, corticosteroids, or immunosuppressive drugs
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- •Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- •Has any active infection requiring systemic therapy
- •Will be on flucytosine at the time of enrollment
- •Has grade ≥ 2 peripheral sensory neuropathy
- •Has poorly controlled diarrhea (e.g., watery stool, uncontrollable bowel movement with drugs, grade ≥ 2 and number of defecations, ≥ 5/day)
- •Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage within 2 weeks prior to enrollment
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the participant, in the opinion of the treating investigator
- •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- •Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
- •Has received prior therapy with an anti-programmed death (PD)-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
- •Has known history of human immunodeficiency virus (HIV) [HIV1/2 antibodies]
- •Has a known history of Hepatitis B
- •Has received live vaccine within 30 days of the planned start of study therapy
- •Is currently participating in and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of trial treatment
研究组 & 干预措施
Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1)
Participants receive pembrolizumab 200 mg every 3 weeks (Q3W) plus oxaliplatin 130 mg/m^2 Q3W by intravenous (IV) infusion plus TS-1 twice daily (BID) by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment will be started on Day 1 of each 3-week course, and will continue for up to ~3 years.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1)
Participants receive pembrolizumab 200 mg every 3 weeks (Q3W) plus oxaliplatin 130 mg/m^2 Q3W by intravenous (IV) infusion plus TS-1 twice daily (BID) by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment will be started on Day 1 of each 3-week course, and will continue for up to ~3 years.
干预措施: Oxaliplatin (Drug)
Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1)
Participants receive pembrolizumab 200 mg every 3 weeks (Q3W) plus oxaliplatin 130 mg/m^2 Q3W by intravenous (IV) infusion plus TS-1 twice daily (BID) by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment will be started on Day 1 of each 3-week course, and will continue for up to ~3 years.
干预措施: TS-1 (Drug)
Pembrolizumab + Cisplatin +TS-1 (Cohort 2)
Participants receive pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment will be started on Day 1 of each 3-week course, and will continue for up to ~3 years.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Cisplatin +TS-1 (Cohort 2)
Participants receive pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment will be started on Day 1 of each 3-week course, and will continue for up to ~3 years.
干预措施: TS-1 (Drug)
Pembrolizumab + Cisplatin +TS-1 (Cohort 2)
Participants receive pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment will be started on Day 1 of each 3-week course, and will continue for up to ~3 years.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Objective Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR)
时间窗: Up to ~36 months
For the primary efficacy analysis, ORR was defined as the percentage of participants who have a best response of complete response (CR, disappearance of all target lesions) or partial response (PR, at least a 30% decrease in the sum of diameters \[SOD\] of target lesions, taking as reference the baseline SOD) per RECIST 1.1 as assessed by BICR.
次要结局
- ORR According to Immune-related Response Evaluation Criteria In Solid Tumors (iRECIST) Assessed by BICR(Up to ~36 months)
- Disease Control Rate (DCR) According to RECIST 1.1 Assessed by BICR(Up to ~36 months)
- Duration of Response (DOR) According to RECIST 1.1 Assessed by BICR(Up to ~36 months)
- Time to Response (TTR) According to RECIST 1.1 Assessed by BICR(Up to ~36 months)
- TTR According to iRECIST 1.1 Assessed by BICR(Up to ~36 months)
- Progression-free Survival (PFS) According to RECIST 1.1 Assessed by BICR(Up to ~36 months)
- DOR According to iRECIST Assessed by BICR(Up to ~36 months)
- DCR According to iRECIST 1.1 Assessed by BICR(Up to ~36 months)
- PFS According to iRECIST 1.1 Assessed by BICR(Up to ~36 months)
- Overall Survival (OS)(Up to ~36 months)
- Number of Participants With ≥1 Adverse Event (AE)(Up to ~36 months)
- Number of Participants Discontinuing From Study Treatment Due to AE(s)(Up to ~36 months)