Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo in Recurrent or Progressive Metastatic Urothelial Carcinoma

Phase 3

Completed

Brief 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Pembrolizumab 200 mg + Epacadostat 100 mg BID	Epacadostat	Pembrolizumab + epacadostat
Pembrolizumab 200 mg + placebo BID	Placebo	Pembrolizumab + placebo
Pembrolizumab 200 mg + placebo BID	Pembrolizumab	Pembrolizumab + placebo
Pembrolizumab 200 mg + Epacadostat 100 mg BID	Pembrolizumab	Pembrolizumab + epacadostat

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo	up to 9 weeks +14 days	ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination.

Secondary Outcome Measures

Name	Time	Method
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE	Up to 8 months	AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs)	Up to 8 months	AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

Locations (135): Ironwood Cancer & Research Centers
🇺🇸
Chandler, Arizona, United States
University of California Irvine Medical Center
🇺🇸
Orange, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸
San Francisco, California, United States
UCLA Hematology Oncology Santa Monica
🇺🇸
Santa Monica, California, United States
Smilow Cancer Center at Yale-New Haven
🇺🇸
New Haven, Connecticut, United States
Northside Hospital, Inc. - GCS/Annex
🇺🇸
Atlanta, Georgia, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
Quincy Medical Group
🇺🇸
Quincy, Illinois, United States
Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
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Ironwood Cancer & Research Centers
🇺🇸Chandler, Arizona, United States