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Perioperative Pembrolizumab (MK-3475) Plus Neoadjuvant Chemotherapy Versus Perioperative Placebo Plus Neoadjuvant Chemotherapy for Cisplatin-eligible Muscle-invasive Bladder Cancer (MIBC) (MK-3475-866 / KEYNOTE-866)

Trial Status: Active

A global study to evaluate peri-operative pembrolizumab with chemotherapy versus placebo to pembrolizumab plus chemotherapy in cisplatin eligible patients.

Inclusion Criteria

  • Have a histologically confirmed diagnosis of muscle invasive bladder cancer (T2-T4aN0M0) with predominant (≥50%) urothelial histology (histology and presence of muscle invasion to be confirmed by BICR): Participants with mixed histology are eligible provided the urothelial component is ≥50%. Participants whose tumors contain any neuroendocrine component are not eligible. Urothelial carcinomas not originating from the bladder (e.g., upper tract [ureters, renal pelvis], urethra) are not eligible.
  • Have clinically non-metastatic bladder cancer (N0M0) determined by imaging (computed tomography (CT) chest or magnetic resonance imaging (MRI) of the abdomen/pelvis.
  • Be deemed eligible for RC + PLND by his/her urologist and/or oncologist and agree to undergo curative intent standard RC + PLND (including prostatectomy if applicable).
  • Have a transurethral resection (TUR) of a bladder tumor that is submitted and adequate to determine histology, muscle invasion, and PD-L1 status by central pathology vendor.
  • Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Have demonstrated adequate organ function.

Exclusion Criteria

  • Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions.
  • Has received any prior systemic anti-neoplastic treatment for MIBC.
  • Is cisplatin-ineligible, as defined by meeting any one of the study criteria.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
  • Has received therapy with hematopoietic growth factor such as granulocyte-colony stimulating factor (G-CSF) or granulocyte-monocyte-colony stimulating factor(GM-CSF) in 14 days prior to randomization.
  • Has received prior systemic anti-cancer therapy including investigational agents within 3 years of randomization.
  • Has received any prior radiotherapy to the bladder.
  • Has received a live vaccine within 30 days prior to the first dose of study drug.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
  • Has hypersensitivity to monoclonal antibodies (mAbs, including pembrolizumab) and/or any of their excipients.
  • Has severe hypersensitivity (≥Grade 3) to cisplatin and/or gemcitabine and any of their excipients.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.

District of Columbia

MedStar Georgetown University Hospital
Status: ACTIVE


Indiana University / Melvin and Bren Simon Cancer Center
Status: ACTIVE
Contact: Sherry Beeler
Phone: 317-278-5627

New Mexico

University of New Mexico Cancer Center
Status: ACTIVE

New York

New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: ACTIVE


Case Comprehensive Cancer Center
Status: ACTIVE


M D Anderson Cancer Center
Status: ACTIVE


Fred Hutch / University of Washington Cancer Consortium
Status: ACTIVE

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Merck and Company Inc

  • Primary ID 3475-866
  • Secondary IDs NCI-2019-03041, 194870, KEYNOTE-866, MK-3475-866, 2018-003808-39
  • ID NCT03924856