NCT02370498已完成3 期
A Phase III, Randomized, Open-label Clinical Trial of Pembrolizumab (MK-3475) Versus Paclitaxel in Subjects With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Who Progressed After First-Line Therapy With Platinum and Fluoropyrimidine
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 592
- 主要终点
- Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) in Programmed Death-Ligand 1 (PD-L1) Positive Participants
研究概览
简要总结
This is a study for participants with advanced gastric or gastroesophageal junction adenocarcinoma who have had tumor progression after first-line treatment with platinum and fluoropyrimidine doublet therapy. The primary study hypotheses are that pembrolizumab (MK-3475) prolongs progression free survival (PFS) and overall survival (OS) for participants with tumors that show positive programmed cell death ligand 1 (PD-L1) expression.
As of 20-March-2016, enrollment will be limited to PD-L1 positive participants.
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
- •Histologically- or cytologically-confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
- •Confirmed metastatic or locally advanced, unresectable disease (by computed tomography [CT] scan or clinical evidence)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Progression on or after prior first-line therapy containing any platinum/fluoropyrimidine doublet
- •Willing to provide tumor tissue for PD-L1 biomarker analysis (new or archived specimens with agreement of Sponsor). As of 20 March 2016, participants must be PD-L1 positive to be enrolled.
- •Human epidermal growth factor receptor 2 (HER-2/neu) status known and participants with HER2/neu positive tumors show documentation of disease progression on treatment containing trastuzumab
- •Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel.
- •Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel.
- •Adequate organ function
排除标准
- •Currently participating and receiving study therapy, or participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of medication
- •Squamous cell or undifferentiated gastric cancer
- •Active autoimmune disease that has required systemic treatment in past 2 years (replacement therapy is not considered a form of systemic treatment
- •Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
- •Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from AEs due to agents administered more than 4 weeks earlier
- •Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent or surgery
- •Known additional malignancy that is progressing or requires active treatment (with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy)
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •History of (noninfectious) pneumonitis that required steroids or current pneumonitis
- •Active infection requiring systemic therapy
- •Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- •Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel.
- •Prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or previously participated in Merck pembrolizumab (MK-3475) clinical trial
- •Known history of human immunodeficiency virus (HIV)
- •Known active Hepatitis B or Hepatitis C
- •Live vaccine within 30 days of planned start of study therapy
- •Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy
研究组 & 干预措施
Pembrolizumab
Experimental
Participants receive 200 mg intravenous (IV) pembrolizumab on Day 1 of each 21-day cycle, for up to 35 administrations (approximately 2 years).
干预措施: pembrolizumab (Biological)
Paclitaxel
Active Comparator
Participants receive 80 mg/m^2 IV paclitaxel on Days 1, 8, and 15 of each 28-day cycle, until disease progression or unacceptable toxicity.
干预措施: paclitaxel (Drug)
结局指标
主要结局
Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) in Programmed Death-Ligand 1 (PD-L1) Positive Participants
时间窗: Up to 30 months (through database cut-off date of 26 Oct 2017)
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval \[CI\]) in months was reported for PD-L1 positive participants by treatment group.
Overall Survival (OS) in PD-L1 Positive Participants
时间窗: Up to 30 months (through database cut-off date of 26 Oct 2017)
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was analyzed using the Kaplan-Meier method and median OS (95% CI) in months was reported for PD-L1 positive participants by treatment group.
次要结局
- PFS According to RECIST 1.1 Based on BICR in All Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- OS in All Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- PFS According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- ORR According to RECIST 1.1 Based on Investigator Assessment in All Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- Duration of Response (DOR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- DOR According to RECIST 1.1 Based on BICR in All Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- DOR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- DOR According to RECIST 1.1 Based on Investigator Assessment in All Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- PFS According to RECIST 1.1 Based on Investigator Assessment in All Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- PFS According to Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) Based on BICR in PD-L1 Positive Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- PFS According to irRECIST Based on BICR in All Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- Time to Tumor Progression (TTP) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- TTP According to RECIST 1.1 Based on BICR in All Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- Objective Response Rate (ORR) According to RECIST 1.1 Based on BICR in PD-L1 Positive Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- ORR According to RECIST 1.1 Based on BICR in All Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- ORR According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- TTP According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- TTP According to RECIST 1.1 Based on Investigator Assessment in All Participants(Up to 30 months (through database cut-off date of 26 Oct 2017))
- Percentage of PD-L1 Positive Participants Who Experienced an Adverse Event (AE)(Up to 71 months (through database cut-off date of 10 Jun 2021))
- Percentage of All Participants Who Experienced an AE(Up to 71 months (through database cut-off date of 10 Jun 2021))
- Percentage of PD-L1 Positive Participants That Discontinued Study Treatment Due to AE(Up to approximately 26.4 months)
- Percentage of All Participants That Discontinued Study Treatment Due to AE(Up to approximately 26.4 months)
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