• Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to 48 months ]
  Progression-free survival is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Progressive Disease (PD) is a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of ≥20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
• Overall Survival (OS) [ Time Frame: Up to 48 months ]
  Overall survival is defined as the time from randomization to death due to any cause.

• Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 43 months ]
  ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: a ≥30% decrease in the sum of diameters [SOD] of target lesions) as assessed by BICR per RECIST 1.1, which is adjusted for this study to allow a maximum of 10 target lesions in total and 5 per organ.
• Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 43 months ]
  For participants who demonstrate a confirmed CR or PR, DOR is the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
• Number of Participants Who Experience One or More Adverse Events (AE) [ Time Frame: Up to approximately 43 months ]
  An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
• Number of Participants Who Discontinued Study Intervention Due to an Adverse Event [ Time Frame: Up to approximately 43 months ]
  An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
• Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 43 months ]
  Progression-free survival is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first.

• Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to 48 months ]
  ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: a ≥30% decrease in the sum of diameters [SOD] of target lesions) as assessed by BICR per RECIST 1.1, which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
• Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to 48 months ]
  For participants who demonstrate confirmed CR or PR, DOR is the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. Complete Response is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response is a ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of ≥20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
• Number of Participants Who Experience One or More Adverse Events (AE) [ Time Frame: Up to 48 months ]
  An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
• Number of Participants Who Discontinued Study Intervention Due to an Adverse Event [ Time Frame: Up to 48 months ]
  An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

• Drug: Pembrolizumab
  Pembrolizumab by intravenous (IV) infusion
  Other Name: MK-3475
• Drug: Gemcitabine
  Gemcitabine by IV infusion
  Other Name: Gemzar
• Drug: Cisplatin
  Cisplatin by IV infusion
  Other Names:

  • Platinol®
  • Platinol®-AQ
• Drug: Placebo
  Placebo to pembrolizumab

• Experimental: Arm A (Pembrolizumab+Gemcitabine+Cisplatin)
  Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
  Interventions:

  • Drug: Pembrolizumab
  • Drug: Gemcitabine
  • Drug: Cisplatin
• Placebo Comparator: Arm B (Placebo+Gemcitabine+Cisplatin)
  Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
  Interventions:

  • Drug: Gemcitabine
  • Drug: Cisplatin
  • Drug: Placebo

Inclusion Criteria

• Has histologically confirmed diagnosis of advanced (metastatic) and/or unresectable (locally advanced) biliary tract cancer (intra-or extrahepatic cholangiocarcinoma or gallbladder cancer)
• Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as determined by the site investigator
• Participants with a history of hepatitis B or hepatitis C can be enrolled if they meet study criteria
• Is able to provide archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion
• Has a life expectancy of greater than 3 months
• Has adequate organ function

Exclusion Criteria

• Has had previous systemic therapy for advanced (metastatic) or unresectable (locally advanced) biliary tract cancer (intra-or extra hepatic cholangiocarcinoma or gallbladder cancer)
• Has ampullary cancer
• Has small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology and/or mucinous cystic neoplasms
• Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti- programmed cell death ligand 1 or 2 (anti-PD-L1, anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
• Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis, as assessed by local site investigator
• Has had an allogenic tissue/solid organ transplant