Pembrolizumab in Combination With Epacadostat or Placebo in Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)

November 17, 2021 updated by: Incyte Corporation

A Phase 3 Randomized, Double-Blind Trial of Pembrolizumab (MK-3475) in Combination With Epacadostat (INCB024360) or Placebo in Participants With Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)

The purpose of this study was to evaluate the efficacy and safety of pembrolizumab + epacadostat vs pembrolizumab + placebo in participants with cisplatin-ineligible urothelial carcinoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

93

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
      • Waratah, New South Wales, Australia, 2298
        • Calvary Mater Newcastle
      • Wollongong, New South Wales, Australia, 2500
        • Southern Medical Day Care Centre
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health-Austin Hospital
  • Belgium
      • Bruxelles, Belgium, 1000
        • Institut Jules Bordet
      • Charleroi, Belgium, 6000
        • Grand Hopital de Charleroi - Site Notre Dame - Oncology
      • Gent, Belgium, 9000
        • Universitair Ziekenhuis Gent
      • Gent, Belgium, 9000
        • AZ Maria Middelares Gent
      • Haine-Saint-Paul, Belgium, 7100
        • Hopital de Jolimont
      • Sint-Niklaas, Belgium, 9100
        • AZ Nikolaas
      • Wilrijk, Belgium, 2610
        • Gza Sint Augustinus
  • Canada
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6Z8
        • Moncton Hospital - Horizon Health Network
    • Ontario
      • Kingston, Ontario, Canada, K7L 2V7
        • Cancer Centre of Southeastern Ontario At Kingston General Hospital
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital Cancer Centre
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Science Centre
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont
      • Québec, Quebec, Canada, G1R 2J6
        • CHU de Quebec - Hotel-Dieu de Quebec
  • France
      • Angers, France, 49055
        • Institut de Cancerologie de l Ouest Site Paul Papin
      • Besançon, France, 25030
        • CHU de Besancon
      • Bordeaux, France, 33076
        • Institut Bergonié
      • Clermont-Ferrand, France, 63011
        • Centre Jean Perrin
      • Marseille, France, 13009
        • Institut Paoli Calmettes
      • Nancy, France, 54100
        • Centre D Oncologie de Gentilly
      • Paris, France, 75908
        • Hopital Europeen Georges Pompidou
      • Pierre-Bénite, France, 69310
        • Centre Hospitalier Lyon Sud
      • Reims, France, 51726
        • Institut Jean Godinot
      • Strasbourg, France, 67091
        • CHU de Strasbourg - Nouvel Hopital Civil
      • Toulouse, France, 31059
        • Institut Claudius Regaud
      • Tours, France, 37044
        • C.H.U. de Tours - Hopital Bretonneau
      • Villejuif, France, 94805
        • Institut Gustave Roussy
  • Germany
      • Duesseldorf, Germany, 40225
        • Universitaetsklinikum Duesseldorf
      • Essen, Germany, 45136
        • Kliniken Essen Mitte
      • 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
      • Trier, Germany, 54292
        • Krankenhaus der Barmherzigen Brueder Trier
      • Tuebingen, Germany, 72076
        • Universitaetsklinikum Tuebingen
    • Schleswig Holstein
      • Luebeck, Schleswig Holstein, Germany, 23538
        • Universitaetsklinikum Schleswig-Holstein. Campus Luebeck
  • Ireland
      • Cork, Ireland
        • Cork University Hospital
      • Dublin, Ireland, 00024
        • Adelaide & Meath Hospital (Incl NCH)
      • Galway, Ireland, H91YR71
        • University College Hospital Galway
      • Limerick, Ireland, V94 F858
        • University Hospital Limerick
      • Waterford, Ireland, X91ER8E
        • University Hospital Waterford
  • Israel
      • Be'er Sheva, Israel, 8410101
        • Soroka Medical Center
      • Haifa, Israel, 31096
        • Rambam Health Care Campus
      • 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
      • Bari, Italy, 70124
        • Istituto Tumori Giovanni Paolo II
      • Meldola, Italy, 47014
        • Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST
      • Milan, Italy, 20133
        • Istituto Nazionale dei Tumori
      • Napoli, Italy, 80131
        • Istituto Nazionale Tumori IRCCS Fondazione Pascale
      • Padova, Italy, 35128
        • Istituto Oncologico Veneto
  • Japan
      • Tokushima, Japan, 770-8503
        • Tokushima University Hospital
      • Tokyo, Japan, 135-8550
        • The Cancer Institute Hospital of JFCR
      • Tokyo, Japan, 113-8519
        • Medical Hospital, Tokyo Medical and Dental University
    • 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
    • Osaka
      • Osakasayama, Osaka, Japan, 589-8511
        • Kindai University Hospital
    • Yamaguchi
      • Ube, Yamaguchi, Japan, 755-8505
        • Yamaguchi University Hospital
  • Korea, Republic of
      • Daejeon, Korea, Republic of, 35015
        • Chungnam National University Hospital
      • 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
      • Eindhoven, Netherlands, 5623 EJ
        • Catharina Ziekenhuis
      • Groningen, Netherlands, 9713 GZ
        • University Medical Center Groningen
      • Rotterdam, Netherlands, 3075 EA
        • Erasmus MC
    • Brabant
      • Breda, Brabant, Netherlands, 4819EV
        • Amphia Ziekenhuis
  • Poland
      • Bielsko-Biala, Poland, 43-300
        • Beskidzkie Centrum Onkologii im. Jana Pawla II
      • Jelenia Góra, Poland, 58-506
        • Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej
      • Katowice, Poland, 40-514
        • Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego
      • Komorowice, Poland, 52-229
        • GLOBE Badania Kliniczne Oddzial we Wroclawiu
      • Otwock, Poland, 05-400
        • Europejskie Centrum Zdrowia Otwock
      • Siedlce, Poland, 08-110
        • Urologica Praktyka Lekarska Adam Marcheluk
      • Szczecin, Poland, 70-111
        • Samodzielny Publiczny Szpital Kliniczny nr 2 PUM w Szczecinie
      • Warszawa, Poland, 01-748
        • Magodent Szpital Elblaska
      • Warszawa, Poland, 02 616
        • Szpital Sw. Elzbiety Mokotowskie Centrum Medyczne
  • 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
      • A Coruña, Spain, 15006
        • Hospital Teresa Herrera - Chuac
      • Badajoz, Spain, 06080
        • Hospital Infanta Cristina
      • Barcelona, Spain, 08035
        • Hospital General Universitari Vall D Hebron
      • Hospitalet de Llobregat, Spain, 08908
        • ICO l Hospitalet
      • Lugo, Spain, 27003
        • Hospital Universitario Lucus Augusti
      • Manresa, Spain, 08243
        • Xarxa Assistencial Universitaria Manresa
      • Sabadell, Spain, 08208
        • Consorci Hospitalari Parc Tauli de Sabadell
      • Sevilla, Spain, 41013
        • Hospital Virgen del Rocío
  • Taiwan
      • Kaohsiung, Taiwan, 833
        • Chang Gung Medical Foundation - Kaohsiung
      • Taichung, Taiwan, 40447
        • China Medical University Hospital
      • Tainan, Taiwan, 704
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital
    • Beitou
      • Taipei, Beitou, Taiwan, 112
        • Taipei Veterans General Hospital
  • Ukraine
      • Dnipropetrovsk, Ukraine, 49102
        • Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC
      • Dnipropetrovsk, Ukraine, 49005
        • MI Dnipr Regional Clinical Hospital named after I.I. Mechnikov
      • Kharkiv, Ukraine, 61000
        • Kharkiv Regional Clinical Oncology Center
      • Kyiv, Ukraine, 03115
        • Kyiv City Clinical Oncology Center
      • Odesa, Ukraine, 65055
        • MI Odessa Regional Oncological Centre
      • Sumy, Ukraine, 40022
        • Rmi Sumy Regional Clinical Oncology Dispensary
  • United Kingdom
      • Glasgow, United Kingdom, G120YN
        • The Beatson West of Scotland Cancer Centre
      • London, United Kingdom, NW3 2QG
        • Royal Free London NHS Foundation Trust
      • London, United Kingdom, EC1A 7BE
        • Barts Health NHS Trust - St Bartholomew's Hospital
      • London, United Kingdom, W6 8RF
        • Imperial College Healthcare NHS Trust
      • 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
      • Tucson, Arizona, United States, 85704
        • Arizona Oncology Associates PC- HOPE
    • California
      • Orange, California, United States, 92868
        • University of California Irvine Medical Center
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Yale Cancer Center
    • Florida
      • Pensacola, Florida, United States, 32503
        • Woodlands Medical Specialists, PA
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Quincy, Illinois, United States, 62301
        • Quincy Medical Group
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • GU Research Network-Urology Cancer Center
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada
    • New York
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Institute
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Willamette Valley Cancer Institute and Research Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19104
        • Abramson Cancer Center of the University of Pennsylvania
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina-Hollings Cancer Center
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Tennessee Oncology, PLLC/The Sarah Cannon Research Institute
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee Medical Center Knoxville
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt-Ingram Cancer Center
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology Nashville
    • Texas
      • Houston, Texas, United States, 77024
        • Texas Oncology-Memorial City
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

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 or cytologically-confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra.
  • Measurable disease based on RECIST v1.1.
  • Be considered ineligible to receive cisplatin-based combination therapy, based on protocol-defined criteria.
  • Have provided tissue for PD-L1 analysis from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
  • Have received no prior systemic chemotherapy for advanced/unresectable (inoperable) or metastatic urothelial cancer.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 within 14 days prior to randomization.
  • Adequate organ function per protocol-defined criteria.

Exclusion Criteria:

  • Disease that is suitable for local therapy administered with curative intent.
  • 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, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  • 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 (hepatitis B surface antigen [HBsAg] reactive) or has active hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.
  • History of a gastrointestinal condition that in the opinion of the Investigator may affect oral drug absorption.
  • History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
  • 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
Experimental: Pembrolizumab 200 mg + epacadostat 100 mg BID
Pembrolizumab + epacadostat
Drug: Pembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
Other Names:
  • MK-3475
Drug: Epacadostat
Epacadostat administered orally twice daily.
Other Names:
  • INCB024360
Active Comparator: Pembrolizumab 200 mg + placebo BID
Pembrolizumab + placebo
Drug: Pembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
Other Names:
  • MK-3475
Drug: Placebo
Matching placebo administered orally twice daily.

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: Week 9
ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination. Responses are based on Investigator assessments per RECIST 1.1 without confirmation using all scans up to the cutoff date.
Week 9

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 approximately 25 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 approximately 25 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 approximately 25 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 approximately 25 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 4, 2017

Primary Completion (Actual)

August 9, 2018

Study Completion (Actual)

August 4, 2020

Study Registration Dates

First Submitted

November 29, 2017

First Submitted That Met QC Criteria

November 29, 2017

First Posted (Actual)

December 5, 2017

Study Record Updates

Last Update Posted (Actual)

December 16, 2021

Last Update Submitted That Met QC Criteria

November 17, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KEYNOTE-672/ECHO-307

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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