Clinical Trials List
Protocol NumberMK3475-061
NCT Number(ClinicalTrials.gov Identfier)NCT02370498
2015-04-01 - 2020-12-31
Phase III
Terminated4
ICD-10C16
Malignant neoplasm of stomach
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
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
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Sponsor
Merck Sharp & Dohme Corp.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Yan-Shen Shan Division of General Surgery
- Wei-Pang Chung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- Chung-Pin Li Division of Hematology & Oncology
- Ming-Huang Chen Division of Hematology & Oncology
- Rheun-Chuan Lee Division of Pediatrics
- Yi-Ping Hung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
2 Terminated
Audit
CRO
Co-Principal Investigator
- Hung-Chih Hsu Division of Hematology & Oncology
- Tsai-Sheng Yang Division of Hematology & Oncology
- Chia-Hsun Hsieh Division of Hematology & Oncology
- Wen-Chi Chou Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
- Wen-Chi Shen Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
3 Terminated
Audit
None
Co-Principal Investigator
- SUNG-HSIN KUO Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- Hsiang-Fong Kao Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
- TA-CHEN HUANG Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- YU-YUN SHAO Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- 林宗哲 Division of Hematology & Oncology
- 呂理駿 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Objectives
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.
Test Drug
Pembrolizumab (MK-3475)
Active Ingredient
Humanized anti-PD-1 mAb
Dosage Form
Injection
Dosage
100 mg/ 4 mL/ vial
Endpoints
Primary Outcome Measures :
1. 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 [ Time Frame: 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.
2. Overall Survival (OS) in PD-L1 Positive Participants [ Time Frame: 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.
1. 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 [ Time Frame: 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.
2. Overall Survival (OS) in PD-L1 Positive Participants [ Time Frame: 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.
Inclution Criteria
Inclusion Criteria:
• 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
• 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
Exclusion Criteria
Exclusion Criteria:
• 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
• 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
The Estimated Number of Participants
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Taiwan
18 participants
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Global
720 participants
