Study of Pembrolizumab (MK-3475) in Participants With Advanced Urothelial Cancer (MK-3475-052/KEYNOTE-052)
Condition: Urothelial Cancer
Intervention: pembrolizumab
Intervention description: IV infusion
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 374.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2); bladder cancer

Summary:

      This is a study using pembrolizumab (MK-3475, KEYTRUDA®) for first-line treatment of
      participants with advanced/unresectable (inoperable) or metastatic urothelial cancer who are
      ineligible for cisplatin-based therapy. The primary study objective is to determine the
      objective response rate (ORR) in all participants and by programmed cell death ligand 1
      (PD-L1) status.

      With Amendment 4, once a participant has achieved the study objective or the study has ended,
      the participant will be discontinued from this study and will be enrolled in an extension
      study to continue protocol-defined assessments and treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically- or cytologically-confirmed diagnosis of advanced/unresectable
             (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or
             urethra (transitional cell and mixed transitional/non-transitional cell histologies)

          -  Ineligible for cisplatin therapy

          -  No prior systemic chemotherapy for metastatic disease (adjuvant or neoadjuvant
             platinum-based chemotherapy with recurrence >12 months since completion of therapy is
             allowed)

          -  Available tissue from a newly obtained core or excisional biopsy of a tumor lesion not
             previously irradiated

          -  Measurable 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; 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 study treatment

          -  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 study
             treatment

        Exclusion Criteria:

          -  Disease that is suitable for local therapy administered with curative intent

          -  Currently participating or has participated in a study of an investigational agent and
             received study therapy or used an investigational device within 4 weeks prior to the
             first dose of study treatment

          -  Prior anti-cancer monoclonal antibody (mAb) for direct anti-neoplastic treatment
             within 4 weeks prior to study Day 1 or who has 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 prior to study Day 1 or not recovered from AEs due to a previously administered
             agent

          -  Known additional malignancy that is progressing or requires active treatment excepting
             basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has
             undergone potentially curative therapy, or in situ cancer

          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

          -  Active autoimmune disease that has required systemic treatment in past 2 years

          -  Evidence of interstitial lung disease or active non-infectious pneumonitis

          -  Active infection requiring systemic therapy

          -  Pregnant or 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 study treatment

          -  Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent
             directed to another co-inhibitory T-cell receptor

          -  Known human immunodeficiency virus (HIV)

          -  Known active Hepatitis B or C

          -  Received a live virus vaccine within 30 days of planned start of study treatment