Pembrolizumab in Combination With Epacadostat or Placebo in Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)
Condition: UC (Urothelial Cancer)
MeSH terms: Carcinoma, Transitional Cell
Intervention: Pembrolizumab; Epacadostat; Placebo
Intervention description: Pembrolizumab administered intravenously every 3 weeks.; Epacadostat administered orally twice daily.; Matching placebo administered orally twice daily.
Intervention MeSH terms: Pembrolizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Masking description: The study will be unblinded after the last participant completes Week 9 imaging assessment for efficacy analysis and after appropriate EC/IRB approvals have been received.
Enrollment: 93.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Urothelial cancer, programmed cell death 1 (PD-1) inhibitor; indoleamine 2,3-dioxygenase (IDO) inhibitor

Summary:

      The purpose of this study was to evaluate the efficacy and safety of pembrolizumab +
      epacadostat vs pembrolizumab + placebo in participants with cisplatin-ineligible urothelial
      carcinoma.
    

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.

          -  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.