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 adults with gastric and gastroesophageal junction (GEJ) adenocarcinoma. The primary study hypotheses are that: * Neoadjuvant and adjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab is superior to neoadjuvant and adjuvant placebo plus chemotherapy, followed by adjuvant placebo in terms of Event-free Survival (EFS) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), and * Neoadjuvant pembrolizumab plus chemotherapy is superior to neoadjuvant placebo plus chemotherapy in terms of rate of Pathological Complete Response (pathCR) at the time of surgery. With Amendment 10, upon study completion, participants will be discontinued and may be enrolled in an extension study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1,007
IV infusion
IV infusion
IV infusion
Oral tablets
IV infusion
IV infusion
IV infusion
IV infusion
City of Hope ( Site 0005)
Duarte, California, United States
Yale Cancer Center ( Site 0016)
New Haven, Connecticut, United States
Georgetown University ( Site 0015)
Washington D.C., District of Columbia, United States
Northwestern University - Robert H. Lurie Comprehensive Cancer Center ( Site 0018)
Chicago, Illinois, United States
The University of Chicago Medical Center ( Site 0004)
Chicago, Illinois, United States
Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP 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.
Time frame: Up to approximately 75 months
Pathological Complete Response (pathCR) Rate - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms
PathCR rate is defined as the percentage of participants having a pathCR based on central review. pathCR is defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes. The percentage of participants having pathCR is presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms.
Time frame: Up to approximately 9 weeks following completion of neoadjuvant treatment (up to Study Week 18)
Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms
OS is defined as the time from randomization to death due to any cause. OS is presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms.
Time frame: Up to approximately 75 months
Number 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 number of participants who experience at least one AE is presented for the Pembrolizumab+FLOT and Placebo+FLOT Cohorts.
Time frame: Up to approximately 70 months
Number of Participants Who Discontinue Study Treatment Due to an 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 number of participants who discontinued study treatment due to an AE is presented for the Pembrolizumab+FLOT and Placebo+FLOT Cohorts.
Time frame: Up to approximately 17 months
Number of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+XP/FP and Placebo+XP/FP 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 number of participants who experience at least one AE will be presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms separately and in combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts.
Time frame: Up to approximately 75 months
Number of Participants Who Discontinue Study Treatment Due to an AE - Pembrolizumab+XP/FP and Placebo+XP/FP 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 number of participants who discontinue study treatment due to an AE will be presented the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms separately and in combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts.
Time frame: Up to approximately 18 months
Disease-free Survival (DFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms
DFS is defined as the time from post-surgery baseline scan until the first occurrence of local or distant recurrence or death from any cause and is based on RECIST 1.1 as assessed by the investigator.
Time frame: Up to approximately 75 months
Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
OS is defined as the time from randomization to death due to any cause. OS is presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms in combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts.
Time frame: Up to approximately 75 months
Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
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Roswell Park Cancer Institute ( Site 0001)
Buffalo, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0019)
New York, New York, United States
Memorial Sloan Kettering ( Site 0024)
New York, New York, United States
Weill Cornell Medical Center ( Site 0023)
New York, New York, United States
University of Rochester ( Site 0011)
Rochester, New York, United States
...and 161 more locations
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 75 months