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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3 Randomized, Double-Blind Clinical Study 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 (KEYNOTE-698/ECHO-303)

Conditions
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UC (Urothelial Cancer)

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: Epacadostat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab 200 mg + Epacadostat 100 mg BID<br>Pembrolizumab + epacadostat | Drug: Pembrolizumab<br>* Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks.<br>* Other names: MK-3475;Drug: Epacadostat<br>* Epacadostat administered orally twice daily.<br>* Other names: INCB024360;|
| Active Comparator: Pembrolizumab 200 mg + placebo BID<br>Pembrolizumab + placebo | Drug: Pembrolizumab<br>* Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks.<br>* Other names: MK-3475;Drug: Placebo<br>* Matching placebo administered orally twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo | 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. | up to 9 weeks +14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs) | 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. | Up to 8 months | 
| Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE | 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. | Up to 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urothelial carcinoma, programmed cell death protein 1 (PD-1) inhibitor, indoleamine 2,3-dioxygenase (IDO) inhibitor