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

November 2, 2021 updated by: Incyte Corporation

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

84

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Kurralta Park, Australia, 5037
        • Adelaide Cancer Centre
      • Macquarie Park, Australia, 2109
        • Macquarie University Hospital
    • New South Wales
      • Wollongong, New South Wales, Australia, 2500
        • Southern Medical Day Care Centre
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health-Austin Hospital
  • Canada
      • Quebec, Canada, G1R 3S1
        • CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
    • Ontario
      • London, Ontario, Canada, N6A 4L6
        • London Health Sciences Centre
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital Cancer Centre
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Research Institute
    • Quebec
      • Montréal, Quebec, Canada, H1T 2M4
        • CIUSSS - Hopital Maisonneuve- Rosemont
      • Montréal, Quebec, Canada, H1T 2M4
        • CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont
      • Québec, Quebec, Canada, G1R 3S1
        • CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
  • Denmark
      • Aalborg, Denmark, 9000
        • Aalborg University Hospital
      • Copenhagen, Denmark, 2100
        • Rigshospitalet
      • Herlev, Denmark, 2730
        • Herlev Hospital
      • Næstved, Denmark, 4700
        • Sjaellands Universitetshospital Naestved
  • France
      • Angers, France, 49055
        • Institut de Cancerologie de l Ouest Site Paul Papin
      • Avignon, France, 84918
        • Clinique Sainte Catherine
      • Caen, France, 14000
        • Centre de Lutte Contre le Cancer François Baclesse
      • Le Mans, France, 72000
        • Clinique Victor Hugo
      • Lille, France, 59020
        • Centre OSCAR LAMBRET
      • Lyon, France, 69008
        • Centre LEON BERARD
      • Montpellier, France, 34298
        • Institut Du Cancer de Montpellier
      • Paris, France, 75014
        • Hopital Cochin
      • Paris, France, 75475
        • Hôpital Saint Louis
      • Reims, France, 51726
        • Institut Jean Godinot
      • Suresnes, France, 92151
        • Centre Médico-Chirurgical Foch
      • Tours, France, 37044
        • C.H.U. de Tours - Hopital Bretonneau
      • Villejuif, France, 94805
        • Institut Gustave Roussy
  • Germany
      • Duesseldorf, Germany, 40225
        • Universitaetsklinikum Duesseldorf
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf
      • Jena, Germany, 07747
        • Universitaetsklinikum Jena
      • Magdeburg, Germany, 39120
        • Universitaetsklinikum Magdeburg A.o.R.
      • Muenchen, Germany, 81675
        • Klinikum rechts der Isar der Technischen Universität
      • Tuebingen, Germany, 72076
        • Universitaetsklinikum Tuebingen
    • Schleswig Holstein
      • Luebeck, Schleswig Holstein, Germany, 23538
        • Universitaetsklinikum Schleswig-Holstein. Campus Luebeck
  • Hungary
      • Budapest, Hungary, 1122
        • Orszagos Onkologiai Intezet
      • Budapest, Hungary, 1145
        • Uzsoki Utcai Kórház
      • Kaposvár, Hungary, 7400
        • Somogy Megyei Kaposi Mór Oktató Kórház
      • Miskolc, Hungary, 3526
        • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
      • Pécs, Hungary, 7624
        • Pecsi Tudomanyegyetem AOK
      • Szolnok, Hungary, 5004
        • Jasz - Nagykun Szolnok megyei Hetenyi Geza Korhaz - Rendelointezet
  • Ireland
      • Cork, Ireland
        • Cork University Hospital
      • Dublin, Ireland, 00024
        • Adelaide & Meath Hospital (Incl NCH)
      • Dublin, Ireland, 00009
        • Beaumont Hospital
      • Galway, Ireland, H91YR71
        • University College Hospital Galway
      • Limerick, Ireland, V94F858
        • University Hospital Limerick
      • Waterford, Ireland, X91ER8E
        • Waterford Regional Hospital
  • Israel
      • Be'er Sheva, Israel, 8410101
        • Soroka Medical Center
      • Haifa, Israel, 31096
        • Rambam Medical Center
      • Kfar Saba, Israel, 4428164
        • Meir Medical Center
      • Petach-Tikwa, Israel, 49100
        • Rabin Medical Center
      • Ramat Gan, Israel, 52621
        • Chaim Sheba Medical Center
      • Tel Aviv, Israel, 6423906
        • Sourasky Medical Center
      • Zerifin, Israel, 70300
        • Assaf Harofeh Medical Center
  • Italy
      • Arezzo, Italy, 52100
        • Medical Oncology Ospedale San Donato
      • Meldola, Italy, 47014
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      • Milano, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Napoli, Italy, 80131
        • Istituto Nazionale Tumori Fondazione Pascale
      • Padova, Italy, 35128
        • Istituto Oncologico Veneto
  • Japan
      • Osaka, Japan, 541-8567
        • Osaka International Cancer Institute
      • Tokyo, Japan, 113-8519
        • Medical Hospital, Tokyo Medical and Dental University
      • Tokyo, Japan, 144-0042
        • Yusen Logistics Co Ltd,. Haneda Logistics Center (MSD DC)
    • Aichi
      • Nagoya, Aichi, Japan, 466-8560
        • Nagoya University Hospital
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
        • National Cancer Center Hospital East
    • Ibaraki
      • Tsukuba, Ibaraki, Japan, 305-8576
        • University of Tsukuba Hospital
    • Nara
      • Kashihara, Nara, Japan, 634-8522
        • Nara Medical University Hospital
    • Yamaguchi
      • Ube, Yamaguchi, Japan, 755-8505
        • Yamaguchi University Hospital
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital Yonsei University Health System
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • VU University Medical Center
      • Amsterdam, Netherlands, 1066 CX
        • Antoni van Leeuwenhoek Ziekenhuis
      • Breda, Netherlands, 4819 EV
        • Amphia Ziekenhuis
      • Eindhoven, Netherlands, 5623 EJ
        • Catharina Ziekenhuis
      • Groningen, Netherlands, 9713 GZ
        • University Medical Center Groningen
  • Russian Federation
      • Ivanovo, Russian Federation, 153013
        • Ivanovo Regional Oncology Dispensary
      • Moscow, Russian Federation, 117997
        • Russian Scientific Center of Roentgenoradiology
      • Moscow, Russian Federation, 115478
        • N.N. Blokhin NMRCO
      • Moscow, Russian Federation, 125284
        • National Medical Research Radiological Centre
      • Ryazan', Russian Federation, 390046
        • Ryazan Regional Clinical Oncology Dispensary
      • Saint Petersburg, Russian Federation, 199106
        • Pokrovskaya City Hospital
      • Ufa, Russian Federation, 450081
        • Clinic of Bashkortostan State Medical University
    • Leningrad Region, Vsevolozhsky District
      • Saint Petersburg, Leningrad Region, Vsevolozhsky District, Russian Federation, 188663
        • Leningrad Regional Oncology Dispensary
  • Spain
      • Barcelona, Spain, 08003
        • Hospital del Mar
      • Barcelona, Spain, 08041
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain, 08035
        • Hospital Vall D Hebron
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Maranon
      • Madrid, Spain, 28033
        • MD Anderson Cancer Center Madrid
      • Málaga, Spain, 29010
        • Hospital Universitario Virgen de la Victoria
      • Santiago De Compostela, Spain, 15706
        • Hospital Clinico Universitario de Santiago
      • Valencia, Spain, 46009
        • Instituto Valenciano de Oncologia
  • Taiwan
      • Kaohsiung, Taiwan, 833
        • Chang Gung Medical Foundation. Kaohsiung Branch
      • Taichung, Taiwan, 40447
        • China Medical University Hospital
      • Tainan, Taiwan, 704
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital
  • Turkey
      • Adana, Turkey, 01370
        • Adana Sehir Hastanesi
      • Ankara, Turkey, 06200
        • Dr. Abdurrahman Yurtaslan Ankara Onkoloji EAH
      • Antalya, Turkey, 07059
        • Akdeniz Universitesi Tip Fakultesi
      • Denizli, Turkey, 20070
        • Pamukkale Unv. Tip Fak.
      • Edirne, Turkey, 22030
        • Trakya Universitesi Tip Fakultesi
      • Istanbul, Turkey, 34899
        • Marmara Universitesi Pendik Arastirma ve Uyg. Hastanesi
      • Samsun, Turkey, 55200
        • Samsun Medical Park Hastanesi
      • İzmir, Turkey, 35340
        • Dokuz Eylul University Faculty of Medicine
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
        • Queen Elizabeth Hospital
      • London, United Kingdom, NW3 2QG
        • Royal Free London NHS Foundation Trust
      • London, United Kingdom, W6 8RF
        • Imperial College Healthcare NHS Trust
      • London, United Kingdom, EC1A 7BE
        • Barts Health NHS Trust - St Bartholomew s Hospital
      • Plymouth, United Kingdom, PL6 8DH
        • Plymouth Hospitals Nhs Trust
      • Sunderland, United Kingdom, SR4 7TP
        • Sunderland Royal Hospital
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • Royal Marsden NHS Trust
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Ironwood Cancer & Research Centers
    • California
      • Orange, California, United States, 92868
        • University of California Irvine Medical Center
      • San Francisco, California, United States, 94158
        • UCSF Helen Diller Family Comprehensive Cancer Center
      • Santa Monica, California, United States, 90404
        • UCLA Hematology Oncology Santa Monica
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Smilow Cancer Center at Yale-New Haven
    • Georgia
      • Atlanta, Georgia, United States, 30341
        • Northside Hospital, Inc. - GCS/Annex
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Quincy, Illinois, United States, 62301
        • Quincy Medical Group
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Health System
    • New York
      • New York, New York, United States, 10016
        • NYU Clinical Cancer Center
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74146
        • Oklahoma Cancer Specialists & Research Institute
    • Oregon
      • Portland, Oregon, United States, 97210
        • Oregon Health & Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina-Hollings Cancer Center
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee Medical Center Knoxville
      • Nashville, Tennessee, United States, 37203
        • Vanderbilt University Medical Center
    • Texas
      • Fort Worth, Texas, United States, 76177
        • US Oncology and Research
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC
      • Norfolk, Virginia, United States, 23502
        • Virginia Oncology Associates
      • Richmond, Virginia, United States, 23298
        • VCU Massey Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
Time Frame: 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.
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)
Time Frame: 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.
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
Time Frame: 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.
Up to 8 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Incyte Corporation

Collaborators

Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 22, 2017

Primary Completion (Actual)

July 27, 2018

Study Completion (Actual)

July 23, 2020

Study Registration Dates

First Submitted

December 11, 2017

First Submitted That Met QC Criteria

December 11, 2017

First Posted (Actual)

December 15, 2017

Study Record Updates

Last Update Posted (Actual)

November 30, 2021

Last Update Submitted That Met QC Criteria

November 2, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KEYNOTE-698/ECHO-303

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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