The purpose of this study is to assess the efficacy and safety of treatment with definitive chemoradiotherapy (dCRT) + pembrolizumab (MK-3475) compared to treatment with dCRT + placebo with respect to Event-free Survival (EFS) and Overall Survival (OS) in: * participants whose tumors express Programmed Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10 * participants whose tumors express PD-L1 CPS ≥1 * all participants The primary study hypotheses are that dCRT+ pembrolizumab is better than dCRT + placebo with respect to: * EFS in participants whose tumors express PD-L1 CPS ≥10 * EFS in participants whose tumors express PD-L1 CPS ≥1 * EFS in all participants * OS in participants whose tumors express PD-L1 CPS ≥10 * OS in participants whose tumors express PD-L1 CPS ≥1 * OS in all participants
Participants receive pembrolizumab or placebo PLUS one of two chemotherapy regimens PLUS radiation therapy for up to approximately one year. The chemotherapy regimens are either: * FP (5-fluorouracil \[5-FU\] + cisplatin) or * FOLFOX (5-FU + oxaliplatin + leucovorin or levoleucovorin).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
703
IV infusion
IV infusion
IV infusion
IV infusion
external radiation
IV infusion
IV infusion
IV infusion
MemorialCare Health System - Long Beach Medical Center-Oncology ( Site 0691)
Long Beach, California, United States
Columbus Regional Research Institute ( Site 0047)
Columbus, Georgia, United States
University of Kansas Cancer Center ( Site 0023)
Westwood, Kansas, United States
Cancer Center of Kansas ( Site 0058)
Wichita, Kansas, United States
University Medical Center ( Site 0035)
New Orleans, Louisiana, United States
Event-free Survival (EFS)
EFS is defined as the time from randomization to an event defined as local, regional, or distant radiological recurrence as assessed by the investigator; clinical recurrence as assessed by the investigator with histopathologic confirmation (in the absence of radiological disease recurrence by investigator assessment); or death from any cause, whichever occurs first.
Time frame: Up to ~60 months
Overall Survival (OS)
OS is defined as the time from randomization to death from any cause.
Time frame: Up to ~72 months
Number of participants with an adverse event (AE)
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time frame: Up to ~15 months
Number of participants discontinuing study treatment due to an adverse event (AE)
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time frame: Up to ~12 months
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Greater Baltimore Medical Center ( Site 0031)
Baltimore, Maryland, United States
Dana Farber Cancer Center ( Site 0034)
Boston, Massachusetts, United States
Henry Ford Hospital ( Site 0685)
Detroit, Michigan, United States
University of Missouri ( Site 0688)
Columbia, Missouri, United States
Renown Regional Medical Center ( Site 0706)
Reno, Nevada, United States
...and 160 more locations