Description:
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.
Title
- Brief Title: Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo in Recurrent or Progressive Metastatic Urothelial Carcinoma
- Official Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
698-00/ECHO-303
- NCT ID:
NCT03374488
Conditions
- Recurrent or Progressive Metastatic Urothelial Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
Pembrolizumab | MK-3475 | Treatment Group 1 |
Epacadostat | INCB024360 | Treatment Group 1 |
Placebo | | Treatment Group 2 |
Purpose
The purpose of this study is 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment Group 1 | Experimental | Pembrolizumab + epacadostat | |
Treatment Group 2 | Active Comparator | Pembrolizumab + placebo | |
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall survival (OS) with pembrolizumab + epacadostat versus pembrolizumab + placebo |
Time Frame: | Up to 27 months |
Safety Issue: | |
Description: | Defined as the time from the date of randomization to the date of death due to any cause. |
Secondary Outcome Measures
Measure: | Objective response rate with pembrolizumab + epacadostat versus pembrolizumab + placebo |
Time Frame: | Approximately 24 months |
Safety Issue: | |
Description: | Defined as the proportion of participants who have a best response of complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination. |
Measure: | Number of participants experiencing adverse events (AEs) compared between pembrolizumab + epacadostat versus pembrolizumab + placebo [Safety and Tolerability] |
Time Frame: | Up to 27 months |
Safety Issue: | |
Description: | 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. |
Measure: | Number of participants discontinuing study treatment due to AEs compared between pembrolizumab + epacadostat versus pembrolizumab + placebo [Safety and Tolerability] |
Time Frame: | Up to 27 months |
Safety Issue: | |
Description: | 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. |
Measure: | Mean change from baseline in global health status/quality of life scales |
Time Frame: | Up to 25 months |
Safety Issue: | |
Description: | Global health status/quality of life scales of the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ)-C30 (items 29 and 30). |
Measure: | Time to true deterioration (TTD) |
Time Frame: | Up to 25 months |
Safety Issue: | |
Description: | Defined as the time from baseline to first onset of patient-reported outcome (PRO) deterioration. |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Incyte Corporation |
Trial Keywords
- Urothelial carcinoma
- programmed cell death protein 1 (PD-1) inhibitor
- indoleamine 2,3-dioxygenase (IDO) inhibitor
Last Updated
January 10, 2018