A Study of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel, or Vinflunine for Participants With Advanced Urothelial Cancer (MK-3475-045/KEYNOTE-045)

Inclusion criteria:

- Histologically- or cytologically-confirmed diagnosis of urothelial cancer of the
renal pelvis, ureter, bladder, or urethra, that is transitional cell or mixed
transitional/non-transitional (predominantly transitional) cell type

- Progression or recurrence of urothelial cancer following a first-line
platinum-containing regimen (cisplatin or carboplatin) for metastatic or inoperable
locally advanced disease; or adjuvant platinum-based therapy following cystectomy for
localized muscle-invasive urothelial cancer with recurrence/progression <=12 months
following completion of therapy; or neoadjuvant platinum-containing therapy prior to
cystectomy for localized muscle-invasive urothelial cancer with recurrence <=12
months following completion of therapy

- No more than 2 prior lines of systemic chemotherapy for urothelial cancer

- Able to provide tissue for biomarker analysis from an archival tissue sample or newly
obtained core or excisional biopsy of a tumor lesion not previously irradiated

- Measureable disease

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Adequate organ function

- Female participants of childbearing potential have a negative urine or serum
pregnancy test; or are surgically sterile, or willing to use 2 acceptable methods of
birth control, or abstain from heterosexual activity for the course of the study
through 120 days after the last dose of pembrolizumab or 180 days after the last dose
of paclitaxel, docetaxel, or vinflunine

- Male participants must be willing to use an adequate method of contraception starting
with the first dose of study medication through 120 days after the last dose of
pembrolizumab or 180 days after the last dose of paclitaxel, docetaxel, or vinflunine

Exclusion criteria:

- Urothelial cancer that is suitable for local therapy administered with curative
intent

- Currently participating in or has participated in a study of an investigational agent
or using an investigational device within 4 weeks prior to the first dose of trial
medication

- Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form
of immunosuppressive therapy within 7 days prior to the first dose of study
medication

- Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2
weeks of study Day 1 or not recovered from adverse events due to a previously
administered agent

- Prior therapy with all choices of active comparator- Known additional malignancy that
is progressing or requires active treatment with the exception of basal cell
carcinoma of the skin, squamous cell carcinoma of the skin that has undergone
potentially curative therapy or in situ cancer; or prostate cancer that was
identified incidentally following cystoprostatectomy for bladder cancer that is Stage
T2N0M0 or lower, Gleason score<= 6, or prostatic-specific antigen (PSA) undetectable

- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

- Active autoimmune disease requiring systemic treatment within the past 3 months or a
documented history of clinically severe autoimmune disease, or a syndrome that
requires systemic or immunosuppressive agents

- Active cardiac disease

- Evidence of interstitial lung disease or active non-infectious pneumonitis

- Active infection requiring systemic therapy

- History of severe hypersensitivity reaction to paclitaxel, docetaxel, or to other
drugs formulated with polysorbate 80 or polyoxyethylated castor oil, or to vinflunine
or other vinca alkaloids

- Requires ongoing therapy with a medication that is a strong inhibitor of the
cytochrome 3A4 (CYP3A4) enzymes

- Pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of pembrolizumab or 180 days after the last dose of paclitaxel,
docetaxel, or vinflunine

- Prior therapy with an anti-programmed cell death 1 (PD-1) or anti-PD-Ligand 1 agent,
or with an agent directed to another co-inhibitory T-cell receptor

- Human immunodeficiency virus (HIV)

- Active hepatitis B or hepatitis C

- Received a live virus vaccine within 30 days of planned start of trial treatment