Back to resultsStudy of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants With Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585/KEYNOTE-585)-China Extension
Primary Purpose
Gastric Cancer, Gastroesophageal Junction Cancer
Status
Active
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Pembrolizumab
Placebo
Cisplatin
Capecitabine
5-fluorouracil
Docetaxel
Oxaliplatin
Leucovorin
Sponsored by
About this trial
This is an interventional treatment trial for Gastric Cancer focused on measuring Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Eligibility Criteria
Inclusion Criteria:
- Has previously untreated localized gastric or gastroesophageal junction (GEJ) adenocarcinoma as defined by T3 or greater primary lesion or the presence of any positive nodes - N+ (clinical nodes) without evidence of metastatic disease.
- Plans to proceed to surgery following pre-operative chemotherapy based on standard staging studies per local practice.
- Is willing to provide tissue from a tumor lesion at baseline and at time of surgery.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 within 3 days prior to the first dose of study treatment.
- Has adequate organ function.
- Male participants of childbearing potential must agree to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy.
- Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
- Has life expectancy of greater than 6 months.
Exclusion Criteria:
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
- Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis factor receptor superfamily member 4 [OX-40], necrosis factor receptor superfamily member 9 [CD137]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.
- Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior the first dose of study treatment.
- Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded.
- Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients, or to any of the study chemotherapy agents and/or to any of their excipients.
- Has an active autoimmune disease that has required systemic treatment in past 2 years.
- Has a known history of human immunodeficiency virus (HIV) infection.
- Has a known history of Hepatitis B or known active Hepatitis C virus infection.
- Has a known history of active tuberculosis (TB).
- Female participants who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
- Male participants who are expecting to father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy.
- Has had an allogenic tissue/solid organ transplant.
- Has received a live vaccine within 30 days prior to the first dose of study treatment.
Sites / Locations
- Afflilated Hospital of Bengbu Medical College-Surgical Oncology (Site 0638)
- Beijing Friendship Hospital ( Site 0637)
- Beijing Cancer Hospital ( Site 0221)
- Fujian Medical University Union Hospital-1 Bingfanglou-Gastric Surgery Department (Site 0632)
- Fujian Provincial Cancer Hospital ( Site 0230)
- The First Affiliated Hospital, Sun Yat-sen University (Site 0635)
- The First Affiliated Hospital of Guangzhou Medical University ( Site 0224)
- Fourth Hospital of Hebei Medical University ( Site 0633)
- Henan Cancer Hospital (Site 0227)
- The Affiliated Hospital of Xuzhou Medical College-Oncology ( Site 0645)
- The First Hospital of Jilin University-Gastrointestinal Surgery ( Site 0234)
- Tangdu Hospital of Fourth Military Medical University of Chinese People's Liberation Army ( Site 0647)
- Shandong Provincial Hospital-Gastrointestinal Surgery ( Site 0640)
- The Affiliated Hospital of Qingdao University ( Site 0636)
- Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 0642)
- Sichuan Cancer hospital
- Zhejiang Provincial People's Hospital-Oncology (Site 0656)
- Zhejiang Cancer Hospital ( Site 0231)
- Sir Run Run Shaw Hospital ( Site 0233)
- The First Affiliated Hospital of Wenzhou Medical University (Site 0652)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Pembrolizumab+Chemotherapy
Placebo+Chemotherapy
Pembrolizumab+FLOT Cohort
Placebo+FLOT Cohort
Arm Description
Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets twice each day (BID) on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5-fluorouracil (5FU) via continuous IV infusion on Days 1 to 5 of each 3-week cycle. Adjuvant: 4 to 10 weeks post-surgery, participants receive pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU via continuous IV infusion on Days 1 to 5 of each 3-week cycle for up to 3 cycles.
Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU via continuous IV infusion on Days 1 to 5 of each 3-week cycle. Adjuvant: 4 to 10 weeks post-surgery, participants receive placebo via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU via continuous IV infusion on Days 1 to 5 of each 3-week cycle for up to 3 cycles.
FLOT=docetaxel+oxaliplatin+5FU+leucovorin (calcium folinate). Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin (calcium folinate) 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations. Adjuvant: 4 to 10 weeks postsurgery, participants receive pembrolizumab 200 mg via IV infusion Day 1 Q3W for up to 11 cycles PLUS docetaxel 50 mg/m^2, oxaliplatin 85 mg/m^2, 5FU 2600 mg/m^2, and leucovorin 200 mg/m^2 Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations.
Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations. Adjuvant: 4 to 10 weeks postsurgery, participants receive placebo via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations.
Outcomes
Primary Outcome Measures
Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms
EFS is based on RECIST 1.1 as assessed by the investigator and is defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by computer tomography (CT) scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), are not considered EFS events.
Pathological Complete Response (pathCR) Rate - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms
PathCR rate is defined as the percentage of participants having a pathCR. pathCR is defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes.
Overall Survival (OS) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms
OS is defined as the time from randomization to death due to any cause.
Percentage of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience at least one AE will be presented.
Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who discontinue study treatment due to an AE will be presented.
Secondary Outcome Measures
Percentage of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms Separately and in Combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience at least one AE will be presented.
Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms Separately and in Combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who discontinue study treatment due to an AE will be presented.
Disease-free Survival (DFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms
DFS is defined as the time from post-surgery baseline scan until the first occurrence of local/distant recurrence or death from any cause and is based on RECIST 1.1 as assessed by the investigator.
Overall Survival (OS) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms and Pembrolizumab+FLOT and Placebo+FLOT Cohorts
OS is defined as the time from randomization to death due to any cause.
Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms and Pembrolizumab+FLOT and Placebo+FLOT Cohorts
EFS is based on RECIST 1.1 as assessed by the investigator and is defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by CT scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), are not considered EFS events.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04882241
Brief Title
Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants With Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585/KEYNOTE-585)-China Extension
Official Title
A Phase III, Randomized, Double-Blind, Clinical Trial of Pembrolizumab (MK-3475) Plus Chemotherapy (XP or FP) Versus Placebo Plus Chemotherapy (XP or FP) as Neoadjuvant/Adjuvant Treatment for Subjects With Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma (KEYNOTE-585)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 29, 2020 (Actual)
Primary Completion Date
February 29, 2024 (Anticipated)
Study Completion Date
February 29, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in the neoadjuvant (prior to surgery) or adjuvant (after surgery) treatment of previously untreated Chinese adults with gastric and gastroesophageal junction (GEJ) adenocarcinoma. No formal hypothesis testing will be done.
Detailed Description
The China extension study will include participants previously enrolled in China in the global study for MK-3475-585 (NCT03221426) plus those enrolled during the China extension enrollment period. A total of approximately 120 Chinese participants will be enrolled.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer, Gastroesophageal Junction Cancer
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blind study
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Pembrolizumab+Chemotherapy
Arm Type
Experimental
Arm Description
Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets twice each day (BID) on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5-fluorouracil (5FU) via continuous IV infusion on Days 1 to 5 of each 3-week cycle.
Adjuvant: 4 to 10 weeks post-surgery, participants receive pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU via continuous IV infusion on Days 1 to 5 of each 3-week cycle for up to 3 cycles.
Arm Title
Placebo+Chemotherapy
Arm Type
Placebo Comparator
Arm Description
Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU via continuous IV infusion on Days 1 to 5 of each 3-week cycle.
Adjuvant: 4 to 10 weeks post-surgery, participants receive placebo via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU via continuous IV infusion on Days 1 to 5 of each 3-week cycle for up to 3 cycles.
Arm Title
Pembrolizumab+FLOT Cohort
Arm Type
Experimental
Arm Description
FLOT=docetaxel+oxaliplatin+5FU+leucovorin (calcium folinate). Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin (calcium folinate) 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations.
Adjuvant: 4 to 10 weeks postsurgery, participants receive pembrolizumab 200 mg via IV infusion Day 1 Q3W for up to 11 cycles PLUS docetaxel 50 mg/m^2, oxaliplatin 85 mg/m^2, 5FU 2600 mg/m^2, and leucovorin 200 mg/m^2 Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations.
Arm Title
Placebo+FLOT Cohort
Arm Type
Placebo Comparator
Arm Description
Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations.
Adjuvant: 4 to 10 weeks postsurgery, participants receive placebo via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations.
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
MK-3475, KEYTRUDA®
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Normal saline solution
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
PLATINOL®
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
XELODA®
Intervention Description
Oral tablets
Intervention Type
Drug
Intervention Name(s)
5-fluorouracil
Other Intervention Name(s)
ADRUCIL®, 5FU
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
TAXOTERE®
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
ELOXATIN®
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
WELLCOVORIN®
Intervention Description
IV infusion
Primary Outcome Measure Information:
Title
Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms
Description
EFS is based on RECIST 1.1 as assessed by the investigator and is defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by computer tomography (CT) scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), are not considered EFS events.
Time Frame
Up to approximately 63 months
Title
Pathological Complete Response (pathCR) Rate - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms
Description
PathCR rate is defined as the percentage of participants having a pathCR. pathCR is defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes.
Time Frame
Up to approximately 15 weeks
Title
Overall Survival (OS) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms
Description
OS is defined as the time from randomization to death due to any cause.
Time Frame
Up to approximately 63 months
Title
Percentage of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts
Description
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience at least one AE will be presented.
Time Frame
Up to approximately 20 months
Title
Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts
Description
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who discontinue study treatment due to an AE will be presented.
Time Frame
Up to approximately 17 months
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms Separately and in Combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
Description
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience at least one AE will be presented.
Time Frame
Up to approximately 20 months
Title
Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms Separately and in Combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
Description
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who discontinue study treatment due to an AE will be presented.
Time Frame
Up to approximately 17 months
Title
Disease-free Survival (DFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms
Description
DFS is defined as the time from post-surgery baseline scan until the first occurrence of local/distant recurrence or death from any cause and is based on RECIST 1.1 as assessed by the investigator.
Time Frame
Up to approximately 63 months
Title
Overall Survival (OS) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms and Pembrolizumab+FLOT and Placebo+FLOT Cohorts
Description
OS is defined as the time from randomization to death due to any cause.
Time Frame
Up to approximately 63 months
Title
Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms and Pembrolizumab+FLOT and Placebo+FLOT Cohorts
Description
EFS is based on RECIST 1.1 as assessed by the investigator and is defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by CT scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), are not considered EFS events.
Time Frame
Up to approximately 63 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has previously untreated localized gastric or gastroesophageal junction (GEJ) adenocarcinoma as defined by T3 or greater primary lesion or the presence of any positive nodes - N+ (clinical nodes) without evidence of metastatic disease.
Plans to proceed to surgery following pre-operative chemotherapy based on standard staging studies per local practice.
Is willing to provide tissue from a tumor lesion at baseline and at time of surgery.
Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 within 3 days prior to the first dose of study treatment.
Has adequate organ function.
Male participants of childbearing potential must agree to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy.
Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
Has life expectancy of greater than 6 months.
Exclusion Criteria:
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
Has an active infection requiring systemic therapy.
Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis factor receptor superfamily member 4 [OX-40], necrosis factor receptor superfamily member 9 [CD137]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.
Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior the first dose of study treatment.
Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded.
Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients, or to any of the study chemotherapy agents and/or to any of their excipients.
Has an active autoimmune disease that has required systemic treatment in past 2 years.
Has a known history of human immunodeficiency virus (HIV) infection.
Has a known history of Hepatitis B or known active Hepatitis C virus infection.
Has a known history of active tuberculosis (TB).
Female participants who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
Male participants who are expecting to father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy.
Has had an allogenic tissue/solid organ transplant.
Has received a live vaccine within 30 days prior to the first dose of study treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Afflilated Hospital of Bengbu Medical College-Surgical Oncology (Site 0638)
City
Bengbu
State/Province
Anhui
ZIP/Postal Code
233004
Country
China
Facility Name
Beijing Friendship Hospital ( Site 0637)
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100050
Country
China
Facility Name
Beijing Cancer Hospital ( Site 0221)
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Facility Name
Fujian Medical University Union Hospital-1 Bingfanglou-Gastric Surgery Department (Site 0632)
City
Fuzhou Fujian
State/Province
Fujian
ZIP/Postal Code
350001
Country
China
Facility Name
Fujian Provincial Cancer Hospital ( Site 0230)
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350014
Country
China
Facility Name
The First Affiliated Hospital, Sun Yat-sen University (Site 0635)
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Facility Name
The First Affiliated Hospital of Guangzhou Medical University ( Site 0224)
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510120
Country
China
Facility Name
Fourth Hospital of Hebei Medical University ( Site 0633)
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
050035
Country
China
Facility Name
Henan Cancer Hospital (Site 0227)
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450008
Country
China
Facility Name
The Affiliated Hospital of Xuzhou Medical College-Oncology ( Site 0645)
City
Xuzhou
State/Province
Jiangsu
ZIP/Postal Code
221006
Country
China
Facility Name
The First Hospital of Jilin University-Gastrointestinal Surgery ( Site 0234)
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Facility Name
Tangdu Hospital of Fourth Military Medical University of Chinese People's Liberation Army ( Site 0647)
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710038
Country
China
Facility Name
Shandong Provincial Hospital-Gastrointestinal Surgery ( Site 0640)
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250001
Country
China
Facility Name
The Affiliated Hospital of Qingdao University ( Site 0636)
City
Qingdao
State/Province
Shandong
ZIP/Postal Code
266003
Country
China
Facility Name
Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 0642)
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200127
Country
China
Facility Name
Sichuan Cancer hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
Zhejiang Provincial People's Hospital-Oncology (Site 0656)
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310014
Country
China
Facility Name
Zhejiang Cancer Hospital ( Site 0231)
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310022
Country
China
Facility Name
Sir Run Run Shaw Hospital ( Site 0233)
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
430030
Country
China
Facility Name
The First Affiliated Hospital of Wenzhou Medical University (Site 0652)
City
Wenzhou
State/Province
Zhejiang
ZIP/Postal Code
32500
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
https://merckclinicaltrials.com/
Description
Merck Clinical Trials Information
Learn more about this trial
Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants With Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585/KEYNOTE-585)-China Extension
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