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

NCT ID: NCT03374488

Last Updated: 2025-08-22

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-22

Study Completion Date

2020-07-23

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.

Detailed Description

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Conditions

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UC (Urothelial Cancer)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

The study will be unblinded after the last participant completes Week 9 imaging assessment for efficacy analysis and after appropriate EC/IRB approvals have been received.

Study Groups

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Pembrolizumab 200 mg + Epacadostat 100 mg BID

Pembrolizumab + epacadostat

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks.

Epacadostat

Intervention Type DRUG

Epacadostat administered orally twice daily.

Pembrolizumab 200 mg + placebo BID

Pembrolizumab + placebo

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type DRUG

Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks.

Placebo

Intervention Type DRUG

Matching placebo administered orally twice daily.

Interventions

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Pembrolizumab

Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks.

Intervention Type DRUG

Epacadostat

Epacadostat administered orally twice daily.

Intervention Type DRUG

Placebo

Matching placebo administered orally twice daily.

Intervention Type DRUG

Other Intervention Names

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MK-3475 INCB024360

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mark Jones, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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Ironwood Cancer & Research Centers

Chandler, Arizona, United States

Site Status

University of California Irvine Medical Center

Orange, California, United States

Site Status

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

UCLA Hematology Oncology Santa Monica

Santa Monica, California, United States

Site Status

Smilow Cancer Center at Yale-New Haven

New Haven, Connecticut, United States

Site Status

Northside Hospital, Inc. - GCS/Annex

Atlanta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Quincy Medical Group

Quincy, Illinois, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

NYU Clinical Cancer Center

New York, New York, United States

Site Status

Oklahoma Cancer Specialists & Research Institute

Tulsa, Oklahoma, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina-Hollings Cancer Center

Charleston, South Carolina, United States

Site Status

University of Tennessee Medical Center Knoxville

Knoxville, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

US Oncology and Research

Fort Worth, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status

VCU Massey Cancer Center

Richmond, Virginia, United States

Site Status

Southern Medical Day Care Centre

Wollongong, New South Wales, Australia

Site Status

Austin Health-Austin Hospital

Heidelberg, Victoria, Australia

Site Status

Adelaide Cancer Centre

Kurralta Park, , Australia

Site Status

Macquarie University Hospital

Macquarie Park, , Australia

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Site Status

Sunnybrook Research Institute

Toronto, Ontario, Canada

Site Status

CIUSSS - Hopital Maisonneuve- Rosemont

Montreal, Quebec, Canada

Site Status

CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Site Status

CHU de Quebec-Universite Laval-Hotel Dieu de Quebec

Québec, Quebec, Canada

Site Status

Aalborg University Hospital

Aalborg, , Denmark

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Herlev Hospital

Herlev, , Denmark

Site Status

Sjaellands Universitetshospital Naestved

Næstved, , Denmark

Site Status

Institut de Cancerologie de l Ouest Site Paul Papin

Angers, , France

Site Status

Clinique Sainte Catherine

Avignon, , France

Site Status

Centre de Lutte Contre le Cancer Francois Baclesse

Caen, , France

Site Status

Clinique Victor Hugo

Le Mans, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Centre Leon Berard

Lyon, , France

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Institut du Cancer de Montpellier

Montpellier, , France

Site Status

Hopital Cochin

Paris, , France

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Hopital Saint Louis

Paris, , France

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Institut Jean Godinot

Reims, , France

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Centre Medico-Chirurgical Foch

Suresnes, , France

Site Status

C.H.U. de Tours - Hopital Bretonneau

Tours, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Universitaetsklinikum Schleswig-Holstein. Campus Luebeck

Lübeck, Schleswig-Holstein, Germany

Site Status

Universitaetsklinikum Duesseldorf

Düsseldorf, , Germany

Site Status

Universitatsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status

Universitaetsklinikum Jena

Jena, , Germany

Site Status

Universitaetsklinikum Magdeburg A.o.R.

Magdeburg, , Germany

Site Status

Klinikum rechts der Isar der Technischen Universitat

München, , Germany

Site Status

Universitaetsklinikum Tuebingen

Tübingen, , Germany

Site Status

Orszagos Onkologiai Intezet

Budapest, , Hungary

Site Status

Uzsoki Utcai Korhaz

Budapest, , Hungary

Site Status

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvár, , Hungary

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Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz

Miskolc, , Hungary

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Pecsi Tudomanyegyetem AOK

Pécs, , Hungary

Site Status

Jasz - Nagykun Szolnok megyei Hetenyi Geza Korhaz - Rendelointezet

Szolnok, , Hungary

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Cork University Hospital

Cork, , Ireland

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Beaumont Hospital

Dublin, , Ireland

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Adelaide & Meath Hospital (Incl NCH)

Dublin, , Ireland

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University College Hospital Galway

Galway, , Ireland

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University Hospital Limerick

Limerick, , Ireland

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Waterford Regional Hospital

Waterford, , Ireland

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Soroka Medical Center

Beersheba, , Israel

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Rambam Medical Center

Haifa, , Israel

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Meir Medical Center

Kfar Saba, , Israel

Site Status

Rabin Medical Center

Petah Tikva, , Israel

Site Status

Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Assaf Harofeh Medical Center

Ẕerifin, , Israel

Site Status

Medical Oncology Ospedale San Donato

Arezzo, , Italy

Site Status

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, , Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status

Istituto Nazionale Tumori Fondazione Pascale

Napoli, , Italy

Site Status

Istituto Oncologico Veneto

Padua, , Italy

Site Status

Nagoya University Hospital

Nagoya, Aichi-ken, Japan

Site Status

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Site Status

University of Tsukuba Hospital

Tsukuba, Ibaraki, Japan

Site Status

Nara Medical University Hospital

Kashihara, Nara, Japan

Site Status

Yamaguchi University Hospital

Ube, Yamaguchi, Japan

Site Status

Osaka International Cancer Institute

Osaka, , Japan

Site Status

Medical Hospital, Tokyo Medical And Dental University

Tokyo, , Japan

Site Status

Yusen Logistics Co Ltd,. Haneda Logistics Center (MSD DC)

Tokyo, , Japan

Site Status

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

Site Status

VU University Medical Center

Amsterdam, , Netherlands

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Amphia Ziekenhuis

Breda, , Netherlands

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Catharina Ziekenhuis

Eindhoven, , Netherlands

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University Medical Center Groningen

Groningen, , Netherlands

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Leningrad Regional Oncology Dispensary

Saint Petersburg, Leningrad Region, Vsevolozhsky District, Russia

Site Status

Ivanovo Regional Oncology Dispensary

Ivanovo, , Russia

Site Status

N.N. Blokhin NMRCO

Moscow, , Russia

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Russian Scientific Center of Roentgenoradiology

Moscow, , Russia

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National Medical Research Radiological Centre

Moscow, , Russia

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Ryazan Regional Clinical Oncology Dispensary

Ryazan, , Russia

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Pokrovskaya City Hospital

Saint Petersburg, , Russia

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Clinic of Bashkortostan State Medical University

Ufa, , Russia

Site Status

Seoul National University Hospital

Seoul, , South Korea

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Severance Hospital Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

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Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital del Mar

Barcelona, , Spain

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Hospital Vall D Hebron

Barcelona, , Spain

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Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

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Hospital General Universitario Gregorio Maranon

Madrid, , Spain

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MD Anderson Cancer Center Madrid

Madrid, , Spain

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Hospital Universitario Virgen de la Victoria

Málaga, , Spain

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Hospital Clinico Universitario de Santiago

Santiago de Compostela, , Spain

Site Status

Instituto Valenciano de Oncologia

Valencia, , Spain

Site Status

Chang Gung Medical Foundation. Kaohsiung Branch

Kaohsiung City, , Taiwan

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China Medical University Hospital

Taichung, , Taiwan

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National Cheng Kung University Hospital

Tainan City, , Taiwan

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National Taiwan University Hospital

Taipei, , Taiwan

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Taipei Veterans General Hospital

Taipei, , Taiwan

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Adana Sehir Hastanesi

Adana, , Turkey (Türkiye)

Site Status

Dr. Abdurrahman Yurtaslan Ankara Onkoloji EAH

Ankara, , Turkey (Türkiye)

Site Status

Akdeniz Universitesi Tip Fakultesi

Antalya, , Turkey (Türkiye)

Site Status

Pamukkale Unv. Tip Fak.

Denizli, , Turkey (Türkiye)

Site Status

Trakya Universitesi Tip Fakultesi

Edirne, , Turkey (Türkiye)

Site Status

Marmara Universitesi Pendik Arastirma ve Uyg. Hastanesi

Istanbul, , Turkey (Türkiye)

Site Status

Dokuz Eylul University Faculty of Medicine

Izmir, , Turkey (Türkiye)

Site Status

Samsun Medical Park Hastanesi

Samsun, , Turkey (Türkiye)

Site Status

Royal Marsden NHS Trust

Sutton, Surrey, United Kingdom

Site Status

Queen Elizabeth Hospital

Birmingham, , United Kingdom

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Barts Health NHS Trust - St Bartholomew s Hospital

London, , United Kingdom

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Royal Free London NHS Foundation Trust

London, , United Kingdom

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Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status

Plymouth Hospitals NHS Trust

Plymouth, , United Kingdom

Site Status

Sunderland Royal Hospital

Sunderland, , United Kingdom

Site Status

Countries

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United States Australia Canada Denmark France Germany Hungary Ireland Israel Italy Japan Netherlands Russia South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

References

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Cicin I, Plimack ER, Gurney H, Leibowitz R, Alekseev BY, Parnis FX, Peer A, Necchi A, Bellmunt J, Nishiyama H, Clark J, Munteanu M, Kataria R, Jia C, Powles T, Sternberg CN. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab for advanced urothelial carcinoma: results from the randomized phase III ECHO-303/KEYNOTE-698 study. BMC Cancer. 2024 Jul 25;23(Suppl 1):1256. doi: 10.1186/s12885-023-11213-6.

Reference Type DERIVED
PMID: 39054485 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2017-002310-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KEYNOTE-698/ECHO-303

Identifier Type: -

Identifier Source: org_study_id

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