Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo in Recurrent or Progressive Metastatic Urothelial Carcinoma
Condition: UC (Urothelial Cancer)
MeSH terms: Carcinoma; Carcinoma, Transitional Cell
Intervention: Pembrolizumab; Epacadostat; Placebo
Intervention description: Pembrolizumab administered intravenously Day 1 of each cycle 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: 84.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Urothelial carcinoma; programmed cell death protein 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 as a treatment for recurrent or progressive metastatic
      urothelial carcinoma in patients who have failed a first-line platinum-containing
      chemotherapy regimen for advanced/metastatic disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically-confirmed diagnosis of urothelial carcinoma 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 carcinoma following one prior platinum
             containing chemotherapy regimen for metastatic or unresectable locally advanced
             disease. A participant who receives a neoadjuvant or adjuvant platinum-containing
             regimen following cystectomy for localized muscle-invasive urothelial carcinoma is
             acceptable (without further systemic treatment), if recurrence/progression occurs ≤ 12
             months following completion of therapy.

          -  Measurable disease based on RECIST v1.1.

          -  Have provided an archival tumor tissue sample or newly obtained core or excisional
             biopsy of a tumor lesion not previously irradiated for PD-L1 analysis.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Adequate organ function per protocol-defined criteria.

        Exclusion Criteria:

          -  Urothelial carcinoma that is suitable for local therapy with curative intent.

          -  History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's
             opinion, is clinically meaningful.

          -  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.

          -  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 (HBsAg reactive) or has active
             hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.

          -  Use of protocol-defined prior/concomitant therapy.