Pembrolizumab in Combination With Epacadostat or Placebo in Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)

Inclusion Criteria:

* Histologically or cytologically-confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra.
* Measurable disease based on RECIST v1.1.
* Be considered ineligible to receive cisplatin-based combination therapy, based on protocol-defined criteria.
* Have provided tissue for PD-L1 analysis from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
* Have received no prior systemic chemotherapy for advanced/unresectable (inoperable) or metastatic urothelial cancer.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 within 14 days prior to randomization.
* Adequate organ function per protocol-defined criteria.

Exclusion Criteria:

* Disease that is suitable for local therapy administered with curative intent.
* Known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
* Active autoimmune disease that has required systemic treatment in past 2 years.
* Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority.
* Known history of or is positive for active hepatitis B (hepatitis B surface antigen \[HBsAg\] reactive) or has active hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.
* History of a gastrointestinal condition that in the opinion of the Investigator may affect oral drug absorption.
* History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
* Use of protocol-defined prior/concomitant therapy.