A global, randomized phase III study to evaluate perioperative pembrolizumab with radical cystectomy + pelvic lymph node dissection (RC+PLND) versus RC+PLND alone in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC).



Eligible Ages
Over 18 Years
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

  • Histologically confirmed diagnosis of muscle invasive bladder cancer (T2-T4aN0M0) with predominant (≥50%) urothelial histology. Participants with mixed histology are eligible provided the urothelial component is ≥50%. Urothelial carcinomas not originating from the bladder are not eligible. Participants whose tumors contain any neuroendocrine component are not eligible.
  • Clinically non-metastatic bladder cancer determined by imaging
  • Eligible for radical cystectomy (RC) + pelvic lymph node dissection (PLND ), and agreement to undergo curative intent standard RC + PLND (including prostatectomy if applicable)
  • Ineligible for treatment with cisplatin, as defined by meeting at least one of the following criteria:
  • Impaired renal function with measured or calculated CrCl 30 to 59 mL/min
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 2
  • Common Terminology Criteria for Adverse Events (CTCAE) v.4 Grade ≥2 audiometric hearing loss
  • CTCAE v.4 Grade ≥2 peripheral neuropathy
  • New York Heart Association (NYHA) Class III heart failure
  • Transurethral resection (TUR) of a bladder tumor that is submitted and adequate for evaluation of histology, muscle invasion and PD-L1 status
  • ECOG performance status of 0, 1, or 2
  • Adequate organ function

Exclusion Criteria

  • Known additional non-urothelial malignancy that is progressing or has required active treatment ≤3 years of study randomization, with certain exceptions
  • Received any prior systemic anti-neoplastic treatment for muscle-invasive bladder cancer (MIBC)
  • Received prior therapy with a anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed cell death 1 ligand 2 (PD-L2), or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
  • Received prior systemic anti-cancer therapy including investigational agents within 3 years prior to randomization
  • Received any prior radiotherapy to the bladder
  • Received a live vaccine within 30 days prior to the first dose of study drug
  • Current participation in or participation in a study of an investigational agent or use of an investigational device within 4 weeks prior to the first dose of study intervention
  • Diagnosis of immunodeficiency or receipt of chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
  • Hypersensitivity to monoclonal antibodies (including pembrolizumab) and/or any of their excipients
  • Active autoimmune disease that has required systemic therapy in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic therapy and is allowed.
  • History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
  • Active infection requiring systemic therapy

Study Design

Phase 3
Study Type
Intervention Model
Parallel Assignment
Primary Purpose
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Pembrolizumab + Surgery
Participants receive 3 preoperative cycles of pembrolizumab, followed by standard of care surgery, followed by up to 14 cycles of postoperative pembrolizumab.
  • Drug: Pembrolizumab
    Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle
    Other names:
    • MK-3475
  • Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])
    Surgical RC+PLND will be done in accordance with the American Urological Association (AUA)/American Society of Clinical Oncology (ASCO)/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) guidelines.
Active Comparator
Surgery alone
Participants receive standard of care surgery alone.
  • Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])
    Surgical RC+PLND will be done in accordance with the American Urological Association (AUA)/American Society of Clinical Oncology (ASCO)/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) guidelines.

Recruiting Locations

Georgetown University Medical Center ( Site 0022)
Washington, District of Columbia 20007
Study Coordinator

More Details

Merck Sharp & Dohme Corp.

Study Contact

Toll Free Number


Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.