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

NCT ID: NCT03361865

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-04
• Study Completion Date: 2020-08-04

Brief Summary

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.

Conditions

UC (Urothelial Cancer)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab 200 mg + epacadostat 100 mg BID

Pembrolizumab + epacadostat

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab administered intravenously 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 every 3 weeks.

Placebo

Intervention Type: DRUG

Matching placebo administered orally twice daily.

Interventions

Pembrolizumab

Pembrolizumab administered intravenously 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

MK-3475; INCB024360

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Incyte Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Jones, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

Arizona Oncology Associates PC- HOPE

Tucson, Arizona, United States

University of California Irvine Medical Center

Orange, California, United States

Yale Cancer Center

New Haven, Connecticut, United States

Woodlands Medical Specialists, PA

Pensacola, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

Quincy Medical Group

Quincy, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

GU Research Network-Urology Cancer Center

Omaha, Nebraska, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, United States

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Medical University of South Carolina-Hollings Cancer Center

Charleston, South Carolina, United States

Tennessee Oncology, PLLC/The Sarah Cannon Research Institute

Chattanooga, Tennessee, United States

University of Tennessee Medical Center Knoxville

Knoxville, Tennessee, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Tennessee Oncology Nashville

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Texas Oncology-Memorial City

Houston, Texas, United States

University of Washington

Seattle, Washington, United States

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Southern Medical Day Care Centre

Wollongong, New South Wales, Australia

Austin Health-Austin Hospital

Heidelberg, Victoria, Australia

Adelaide Cancer Centre

Kurralta Park, , Australia

Macquarie University Hospital

Macquarie Park, , Australia

Institut Jules Bordet

Brussels, , Belgium

Grand Hopital de Charleroi - Site Notre Dame - Oncology

Charleroi, , Belgium

AZ Maria Middelares Gent

Ghent, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Hopital de Jolimont

Haine-Saint-Paul, , Belgium

AZ Nikolaas

Sint-Niklaas, , Belgium

GZA Sint Augustinus

Wilrijk, , Belgium

Moncton Hospital - Horizon Health Network

Moncton, New Brunswick, Canada

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Sunnybrook Health Science Centre

Toronto, Ontario, Canada

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

Montreal, Quebec, Canada

CHU de Quebec - Hotel-Dieu de Quebec

Québec, Quebec, Canada

Institut de Cancerologie de l Ouest Site Paul Papin

Angers, , France

CHU de Besancon

Besançon, , France

Institut Bergonie

Bordeaux, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Institut Paoli Calmettes

Marseille, , France

Centre d Oncologie de Gentilly

Nancy, , France

Hopital Europeen Georges Pompidou

Paris, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Institut Jean Godinot

Reims, , France

CHU de Strasbourg - Nouvel Hopital Civil

Strasbourg, , France

Institut Claudius Regaud

Toulouse, , France

C.H.U. de Tours - Hopital Bretonneau

Tours, , France

Institut Gustave Roussy

Villejuif, , France

Universitaetsklinikum Schleswig-Holstein. Campus Luebeck

Lübeck, Schleswig-Holstein, Germany

Universitaetsklinikum Duesseldorf

Düsseldorf, , Germany

Kliniken Essen Mitte

Essen, , Germany

Universitatsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Universitaetsklinikum Jena

Jena, , Germany

Universitaetsklinikum Magdeburg A.o.R.

Magdeburg, , Germany

Klinikum rechts der Isar der Technischen Universitat

München, , Germany

Krankenhaus der Barmherzigen Brueder Trier

Trier, , Germany

Universitaetsklinikum Tuebingen

Tübingen, , Germany

Cork University Hospital

Cork, , Ireland

Adelaide & Meath Hospital (Incl NCH)

Dublin, , Ireland

University College Hospital Galway

Galway, , Ireland

University Hospital Limerick

Limerick, , Ireland

University Hospital Waterford

Waterford, , Ireland

Soroka Medical Center

Beersheba, , Israel

Rambam Health Care Campus

Haifa, , Israel

Meir Medical Center

Kfar Saba, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

Sourasky Medical Center

Tel Aviv, , Israel

Assaf Harofeh Medical Center

Ẕerifin, , Israel

Medical Oncology Ospedale San Donato

Arezzo, , Italy

Istituto Tumori Giovanni Paolo II

Bari, , Italy

Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST

Meldola, , Italy

Istituto Nazionale dei Tumori

Milan, , Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, , Italy

Istituto Oncologico Veneto

Padua, , Italy

Nagoya University Hospital

Nagoya, Aichi-ken, Japan

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

University of Tsukuba Hospital

Tsukuba, Ibaraki, Japan

Nara Medical University Hospital

Kashihara, Nara, Japan

Kindai University Hospital

Sayama, Osaka, Japan

Yamaguchi University Hospital

Ube, Yamaguchi, Japan

Tokushima University Hospital

Tokushima, , Japan

Medical Hospital, Tokyo Medical And Dental University

Tokyo, , Japan

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

Amphia Ziekenhuis

Breda, North Brabant, Netherlands

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

VU University Medical Center

Amsterdam, , Netherlands

Catharina Ziekenhuis

Eindhoven, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Beskidzkie Centrum Onkologii im. Jana Pawla II

Bielsko-Biala, , Poland

Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej

Jelenia Góra, , Poland

Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego

Katowice, , Poland

GLOBE Badania Kliniczne Oddzial we Wroclawiu

Komorowice, , Poland

Europejskie Centrum Zdrowia Otwock

Otwock, , Poland

Urologica Praktyka Lekarska Adam Marcheluk

Siedlce, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie

Szczecin, , Poland

Magodent Szpital Elblaska

Warsaw, , Poland

Szpital Sw. Elzbiety Mokotowskie Centrum Medyczne

Warsaw, , Poland

Leningrad Regional Oncology Dispensary

Saint Petersburg, Leningrad Region, Vsevolozhsky District, Russia

Ivanovo Regional Oncology Dispensary

Ivanovo, , Russia

N.N. Blokhin NMRCO

Moscow, , Russia

Russian Scientific Center of Roentgenoradiology

Moscow, , Russia

National Medical Research Radiological Centre

Moscow, , Russia

Ryazan Regional Clinical Oncology Dispensary

Ryazan, , Russia

Pokrovskaya City Hospital

Saint Petersburg, , Russia

Clinic of Bashkortostan State Medical University

Ufa, , Russia

Chungnam National University Hospital

Daejeon, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hospital Teresa Herrera - Chuac

A Coruña, , Spain

Hospital Infanta Cristina

Badajoz, , Spain

Hospital General Universitari Vall d Hebron

Barcelona, , Spain

ICO L Hospitalet

L'Hospitalet de Llobregat, , Spain

Hospital Universitario Lucus Augusti

Lugo, , Spain

Xarxa Assistencial Universitaria Manresa

Manresa, , Spain

Consorci Hospitalari Parc Tauli de Sabadell

Sabadell, , Spain

Hospital Virgen del Rocio

Seville, , Spain

Taipei Veterans General Hospital

Taipei, Beitou, Taiwan

Chang Gung Medical Foundation - Kaohsiung

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

MI Dnipr Regional Clinical Hospital named after I.I. Mechnikov

Dnipropetrovsk, , Ukraine

Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC

Dnipropetrovsk, , Ukraine

Kharkiv Regional Clinical Oncology Center

Kharkiv, , Ukraine

Kyiv City Clinical Oncology Center

Kyiv, , Ukraine

MI Odessa Regional Oncological Centre

Odesa, , Ukraine

RMI Sumy Regional Clinical Oncology Dispensary

Sumy, , Ukraine

Royal Marsden NHS Trust

Sutton, Surrey, United Kingdom

The Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Barts Health NHS Trust - St Bartholomew's Hospital

London, , United Kingdom

Royal Free London NHS Foundation Trust

London, , United Kingdom

Imperial College Healthcare NHS Trust

London, , United Kingdom

Plymouth Hospitals NHS Trust

Plymouth, , United Kingdom

Sunderland Royal Hospital

Sunderland, , United Kingdom

Countries

United States; Australia; Belgium; Canada; France; Germany; Ireland; Israel; Italy; Japan; Netherlands; Poland; Russia; South Korea; Spain; Taiwan; Ukraine; United Kingdom

References

Necchi A, Van der Heijden MS, Trukhin D, Peer A, Gurney H, Alekseev BY, Parnis FX, Leibowitz R, De Santis M, Grivas P, Clark J, Munteanu M, Kataria R, Jia C, Balar AV, de Wit R. Pembrolizumab plus either epacadostat or placebo for cisplatin-ineligible urothelial carcinoma: results from the ECHO-307/KEYNOTE-672 study. BMC Cancer. 2024 Jul 25;23(Suppl 1):1252. doi: 10.1186/s12885-023-10727-3.

Reference Type: DERIVED

PMID: 39054491 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2017-002311-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KEYNOTE-672/ECHO-307

Identifier Type: -

Identifier Source: org_study_id