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

NCT03361865 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: KEYNOTE-672/ECHO-3072017-002311-34
• Study Type: interventional
• Target: 93
• Locations: 18 countries
• Sites: 143

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)

Keywords

Urothelial cancer, programmed cell death 1 (PD-1) inhibitor; indoleamine 2,3-dioxygenase (IDO) inhibitor

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo

  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 Outcomes (2)

• Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs)

  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

  Up to approximately 25 months

Study Arms (2)

Pembrolizumab 200 mg + epacadostat 100 mg BID

EXPERIMENTAL

Pembrolizumab + epacadostat

Drug: Pembrolizumab; Drug: Epacadostat

Pembrolizumab 200 mg + placebo BID

ACTIVE COMPARATOR

Pembrolizumab + placebo

Drug: Pembrolizumab; Drug: Placebo

Interventions

Pembrolizumab DRUG

Pembrolizumab administered intravenously every 3 weeks.

Also known as: MK-3475

Pembrolizumab 200 mg + epacadostat 100 mg BID; Pembrolizumab 200 mg + placebo BID

Epacadostat DRUG

Epacadostat administered orally twice daily.

Also known as: INCB024360

Pembrolizumab 200 mg + epacadostat 100 mg BID

Placebo DRUG

Matching placebo administered orally twice daily.

Pembrolizumab 200 mg + placebo BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (143)

Arizona Oncology Associates PC- HOPE

Tucson, Arizona, 85704, United States

Location

University of California Irvine Medical Center

Orange, California, 92868, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06511, United States

Location

Woodlands Medical Specialists, PA

Pensacola, Florida, 32503, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Quincy Medical Group

Quincy, Illinois, 62301, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

GU Research Network-Urology Cancer Center

Omaha, Nebraska, 68130, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, 97401, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Medical University of South Carolina-Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Tennessee Oncology, PLLC/The Sarah Cannon Research Institute

Chattanooga, Tennessee, 37404, United States

Location

University of Tennessee Medical Center Knoxville

Knoxville, Tennessee, 37920, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology Nashville

Nashville, Tennessee, 37203, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Texas Oncology-Memorial City

Houston, Texas, 77024, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

Southern Medical Day Care Centre

Wollongong, New South Wales, 2500, Australia

Location

Austin Health-Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Adelaide Cancer Centre

Kurralta Park, 5037, Australia

Location

Macquarie University Hospital

Macquarie Park, 2109, Australia

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Grand Hopital de Charleroi - Site Notre Dame - Oncology

Charleroi, 6000, Belgium

Location

AZ Maria Middelares Gent

Ghent, 9000, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Hopital de Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

AZ Nikolaas

Sint-Niklaas, 9100, Belgium

Location

GZA Sint Augustinus

Wilrijk, 2610, Belgium

Location

Moncton Hospital - Horizon Health Network

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Health Science Centre

Toronto, Ontario, M4N 3M5, Canada

Location

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

Montreal, Quebec, H1T 2M4, Canada

Location

CHU de Quebec - Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

Institut de Cancerologie de l Ouest Site Paul Papin

Angers, 49055, France

Location

CHU de Besancon

Besançon, 25030, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Centre d Oncologie de Gentilly

Nancy, 54100, France

Location

Hopital Europeen Georges Pompidou

Paris, 75908, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69310, France

Location

Institut Jean Godinot

Reims, 51726, France

Location

CHU de Strasbourg - Nouvel Hopital Civil

Strasbourg, 67091, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

C.H.U. de Tours - Hopital Bretonneau

Tours, 37044, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Universitaetsklinikum Schleswig-Holstein. Campus Luebeck

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Universitaetsklinikum Duesseldorf

Düsseldorf, 40225, Germany

Location

Kliniken Essen Mitte

Essen, 45136, Germany

Location

Universitatsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitaetsklinikum Jena

Jena, 07747, Germany

Location

Universitaetsklinikum Magdeburg A.o.R.

Magdeburg, 39120, Germany

Location

Klinikum rechts der Isar der Technischen Universitat

München, 81675, Germany

Location

Krankenhaus der Barmherzigen Brueder Trier

Trier, 54292, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, 72076, Germany

Location

Cork University Hospital

Cork, Ireland

Location

Adelaide & Meath Hospital (Incl NCH)

Dublin, 00024, Ireland

Location

University College Hospital Galway

Galway, H91YR71, Ireland

Location

University Hospital Limerick

Limerick, V94 F858, Ireland

Location

University Hospital Waterford

Waterford, X91ER8E, Ireland

Location

Soroka Medical Center

Beersheba, 8410101, Israel

Location

Rambam Health Care Campus

Haifa, 31096, Israel

Location

Meir Medical Center

Kfar Saba, 4428164, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Assaf Harofeh Medical Center

Ẕerifin, 70300, Israel

Location

Medical Oncology Ospedale San Donato

Arezzo, 52100, Italy

Location

Istituto Tumori Giovanni Paolo II

Bari, 70124, Italy

Location

Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST

Meldola, 47014, Italy

Location

Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, 80131, Italy

Location

Istituto Oncologico Veneto

Padua, 35128, Italy

Location

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

University of Tsukuba Hospital

Tsukuba, Ibaraki, 305-8576, Japan

Location

Nara Medical University Hospital

Kashihara, Nara, 634-8522, Japan

Location

Kindai University Hospital

Sayama, Osaka, 589-8511, Japan

Location

Yamaguchi University Hospital

Ube, Yamaguchi, 755-8505, Japan

Location

Tokushima University Hospital

Tokushima, 770-8503, Japan

Location

Medical Hospital, Tokyo Medical And Dental University

Tokyo, 113-8519, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

Location

Amphia Ziekenhuis

Breda, North Brabant, 4819EV, Netherlands

Location

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Catharina Ziekenhuis

Eindhoven, 5623 EJ, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Erasmus MC

Rotterdam, 3075 EA, Netherlands

Location

Beskidzkie Centrum Onkologii im. Jana Pawla II

Bielsko-Biala, 43-300, Poland

Location

Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej

Jelenia Góra, 58-506, Poland

Location

Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego

Katowice, 40-514, Poland

Location

GLOBE Badania Kliniczne Oddzial we Wroclawiu

Komorowice, 52-229, Poland

Location

Europejskie Centrum Zdrowia Otwock

Otwock, 05-400, Poland

Location

Urologica Praktyka Lekarska Adam Marcheluk

Siedlce, 08-110, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie

Szczecin, 70-111, Poland

Location

Magodent Szpital Elblaska

Warsaw, 01-748, Poland

Location

Szpital Sw. Elzbiety Mokotowskie Centrum Medyczne

Warsaw, 02 616, Poland

Location

Leningrad Regional Oncology Dispensary

Saint Petersburg, Leningrad Region, Vsevolozhsky District, 188663, Russia

Location

Ivanovo Regional Oncology Dispensary

Ivanovo, 153013, Russia

Location

N.N. Blokhin NMRCO

Moscow, 115478, Russia

Location

Russian Scientific Center of Roentgenoradiology

Moscow, 117997, Russia

Location

National Medical Research Radiological Centre

Moscow, 125284, Russia

Location

Ryazan Regional Clinical Oncology Dispensary

Ryazan, 390046, Russia

Location

Pokrovskaya City Hospital

Saint Petersburg, 199106, Russia

Location

Clinic of Bashkortostan State Medical University

Ufa, 450081, Russia

Location

Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Teresa Herrera - Chuac

A Coruña, 15006, Spain

Location

Hospital Infanta Cristina

Badajoz, 06080, Spain

Location

Hospital General Universitari Vall d Hebron

Barcelona, 08035, Spain

Location

ICO L Hospitalet

L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27003, Spain

Location

Xarxa Assistencial Universitaria Manresa

Manresa, 08243, Spain

Location

Consorci Hospitalari Parc Tauli de Sabadell

Sabadell, 08208, Spain

Location

Hospital Virgen del Rocio

Seville, 41013, Spain

Location

Taipei Veterans General Hospital

Taipei, Beitou, 112, Taiwan

Location

Chang Gung Medical Foundation - Kaohsiung

Kaohsiung City, 833, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

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

Dnipropetrovsk, 49005, Ukraine

Location

Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC

Dnipropetrovsk, 49102, Ukraine

Location

Kharkiv Regional Clinical Oncology Center

Kharkiv, 61000, Ukraine

Location

Kyiv City Clinical Oncology Center

Kyiv, 03115, Ukraine

Location

MI Odessa Regional Oncological Centre

Odesa, 65055, Ukraine

Location

RMI Sumy Regional Clinical Oncology Dispensary

Sumy, 40022, Ukraine

Location

Royal Marsden NHS Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

The Beatson West of Scotland Cancer Centre

Glasgow, G120YN, United Kingdom

Location

Barts Health NHS Trust - St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W6 8RF, United Kingdom

Location

Plymouth Hospitals NHS Trust

Plymouth, PL6 8DH, United Kingdom

Location

Sunderland Royal Hospital

Sunderland, SR4 7TP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39054491 DERIVED

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; epacadostat

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

855-463-3463

Study Officials

• Mark Jones, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2017
• First Posted: December 5, 2017
• Study Start: December 4, 2017
• Primary Completion: August 9, 2018
• Study Completion: August 4, 2020
• Last Updated: August 22, 2025
• Results First Posted: August 29, 2019

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (13); IE (5); RU (8); CA (6); ES (8); NL (6); BE (7); TW (5); KR (5); IT (6); AU (5); IL (7); JP (9); PL (9); DE (9); UA (6); GB (7); US (22)