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Phase 3 Completed N=1,069 Randomized Triple-blind Treatment

Pembrolizumab (MK-3475) Plus Gemcitabine/Cisplatin Versus Placebo Plus Gemcitabine/Cisplatin for First-Line Advanced and/or Unresectable Biliary Tract Carcinoma (BTC) (MK-3475-966/KEYNOTE-966)

Source: ClinicalTrials.gov NCT04003636 ↗
Enrolled (actual)
1,069
Serious AEs
50.7%
Results posted
Dec 2023
Primary outcomePrimary: Overall Survival (OS) — 12.7; 10.9 Months — p=0.0034
◆ Published Evidence
Highly cited
1,026citations · ~342 / year
Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet (London, England) · 2023 · Open access · High-confidence link

Summary

This is a study of pembrolizumab plus gemcitabine/cisplatin versus placebo plus gemcitabine/cisplatin as first-line therapy in participants with advanced and/or unresectable biliary tract carcinoma. The primary hypothesis is pembrolizumab plus gemcitabine/cisplatin is superior to placebo plus gemcitabine/cisplatin with respect to overall survival (OS).

Linked Publications (5)

  • Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial.
    Lancet (London, England) · 2023 · 1,026 citations · Open access · High-confidence link
  • Cost-effectiveness analysis of pembrolizumab plus chemotherapy as first-line treatment for advanced biliary tract cancer: perspectives from US and Chinese payers.
    BMJ open · 2025 · 3 citations · Open access · Likely link
  • Cost-effectiveness of pembrolizumab plus chemotherapy vs. chemotherapy as first-line treatment for advanced biliary tract cancer in China and the US.
    Frontiers in pharmacology · 2024 · 3 citations · Open access · Likely link
  • First-Line Pembrolizumab Plus Chemotherapy for Advanced Biliary Tract Cancer: China Subgroup Analysis of the Randomized Phase 3 KEYNOTE-966 Study.
    Advances in therapy · 2026 · 0 citations · Likely link
  • Identifying Indications for Neoadjuvant Therapy in Cholangiocarcinoma.
    Oncology (Williston Park, N.Y.) · 2024 · 0 citations · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Overall Survival (OS)
12.7; 10.9 0.0034 sig
SECONDARY
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (BICR)
6.5; 5.6 0.0225 sig
SECONDARY
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
28.7; 28.5 0.4735
SECONDARY
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
8.3; 6.8
SECONDARY
Number of Participants Who Experience One or More Adverse Events (AE)
524; 532
SECONDARY
Number of Participants Who Discontinued Study Intervention Due to an AE
140; 125

Eligibility Criteria

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04003636) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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