Immunotherapy for Bladder Cancer - Keynote 057

Short title

Pembrolizumab (MK-3475) in high risk Non-muscle Invasive Bladder Cancer ( NMIBC) patients unresponsive to Bacillus Calmette-Guerin (BCG)

Long title

A Phase II Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Subjects with High Risk Non-muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG) Therapy.


The purpose of this study is to find meaningful response of Pembrolizumab on high risk NMIBC unresponsive to Bacillus Calmette Guerin (BCG) therapy and who are considered ineligible for or have refused to undergo radical cystectomy. Pembrolizumab is an immunotherapy medicine that works by blocking a molecule called PD-1 that shuts down the immune response. By blocking PD-1 can allow the immune system to detect and attack cancer cells.

Pembrolizumab is already approved to treat melanoma and non-small cell lung cancer, but its use in this study is considered investigational. Patients in this study will receive 200 mg pembrolizumab (MK-3475), intravenously (by vein), every 3 weeks for up to 24 months.

There is currently no standard non-surgical treatment for patients with NMIBC after BCG failure. The standard of care in this patient population is radical cystectomy, a procedure with significant associated morbidity and mortality. Pembrolizumab (MK-3475) has shown some efficacy in heavily pre-treated metastatic bladder cancer. Findings in the bladder cancer POC cohort suggested that subjects with smaller disease burden could be experiencing a greater benefit from therapy – a finding that has been observed in the larger melanoma cohort within the pembrolizumab (MK-3475) program. Evaluating pembrolizumab (MK-3475) in subjects with NMIBC who are unresponsive to BCG and either are ineligible for surgery, or have elected not to undergo the procedure, represents the opportunity to study the benefits of this agent in a population with high unmet need, and relatively small tumor burden.


  • Diagnosis of high risk non-muscle-invasive urothelial carcinoma or bladder cancer
  • Absence of resectable disease after at least 2 cystoscopy /transurethral resection (TURBT) procedures (residual CIS acceptable)
  • BCG-unresponsive high risk non-muscle-invasive bladder cancer after treatment with adequate BCG therapy
  • Ineligible for radical cystectomy or refusal of radical cystectomy
  • Available tissue from a newly obtained core biopsy of a tumor lesion not previously irradiated
  • Adequate organ function
  • Female participants of childbearing potential have a negative urine or serum pregnancy test and must be willing to use an adequate method of contraception
  • Male participants must be willing to use an adequate method of contraception




Timothy Wilson


Steven O’Day

Jenifer Linehan


Bladder cancer