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UC (Urothelial Cancer)Phase 3NCT03374488

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

A Phase 3 study testing Pembrolizumab and Epacadostat in people with UC (Urothelial Cancer), run by Incyte Corporation at 135 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
UC (Urothelial Cancer)
What is being tested?
Pembrolizumab and Epacadostat
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
84 participants
Where
135 sitesin 18 countries
Study dates
22 Dec 2017to 23 Jul 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

135 sites in 18 countries.

135 sites in 18 countries

United States24 sites

  • University of Michigan Health System

    Ann Arbor, Michigan, 48109

  • Northside Hospital, Inc. - GCS/Annex

    Atlanta, Georgia, 30341

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Ironwood Cancer & Research Centers

    Chandler, Arizona, 85224

  • Medical University of South Carolina-Hollings Cancer Center

    Charleston, South Carolina, 29425

  • University of Chicago

    Chicago, Illinois, 60637

  • Virginia Cancer Specialists, PC

    Fairfax, Virginia, 22031

  • US Oncology and Research

    Fort Worth, Texas, 76177

  • University of Tennessee Medical Center Knoxville

    Knoxville, Tennessee, 37920

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37203

  • Smilow Cancer Center at Yale-New Haven

    New Haven, Connecticut, 06510

  • NYU Clinical Cancer Center

    New York, New York, 10016

  • Virginia Oncology Associates

    Norfolk, Virginia, 23502

  • University of California Irvine Medical Center

    Orange, California, 92868

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Oregon Health & Science University

    Portland, Oregon, 97210

  • Quincy Medical Group

    Quincy, Illinois, 62301

  • VCU Massey Cancer Center

    Richmond, Virginia, 23298

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94158

  • UCLA Hematology Oncology Santa Monica

    Santa Monica, California, 90404

  • Oklahoma Cancer Specialists & Research Institute

    Tulsa, Oklahoma, 74146

Other trials in United States

France13 sites

  • Institut de Cancerologie de l Ouest Site Paul Papin

    Angers, 49055

  • Clinique Sainte Catherine

    Avignon, 84918

  • Centre de Lutte Contre le Cancer Francois Baclesse

    Caen, 14000

  • Clinique Victor Hugo

    Le Mans, 72000

  • Centre Oscar Lambret

    Lille, 59020

  • Centre Leon Berard

    Lyon, 69008

  • Institut du Cancer de Montpellier

    Montpellier, 34298

  • Hopital Cochin

    Paris, 75014

  • Hopital Saint Louis

    Paris, 75475

  • Institut Jean Godinot

    Reims, 51726

  • Centre Medico-Chirurgical Foch

    Suresnes, 92151

  • C.H.U. de Tours - Hopital Bretonneau

    Tours, 37044

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Japan8 sites

  • Nara Medical University Hospital

    Kashihara, Nara, 634-8522

  • National Cancer Center Hospital East

    Kashiwa, Chiba, 277-8577

  • Nagoya University Hospital

    Nagoya, Aichi-ken, 466-8560

  • Osaka International Cancer Institute

    Osaka, 541-8567

  • Medical Hospital, Tokyo Medical And Dental University

    Tokyo, 113-8519

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

    Tokyo, 144-0042

  • University of Tsukuba Hospital

    Tsukuba, Ibaraki, 305-8576

  • Yamaguchi University Hospital

    Ube, Yamaguchi, 755-8505

Other trials in Japan

Russia8 sites

  • Ivanovo Regional Oncology Dispensary

    Ivanovo, 153013

  • N.N. Blokhin NMRCO

    Moscow, 115478

  • Russian Scientific Center of Roentgenoradiology

    Moscow, 117997

  • National Medical Research Radiological Centre

    Moscow, 125284

  • Ryazan Regional Clinical Oncology Dispensary

    Ryazan, 390046

  • Leningrad Regional Oncology Dispensary

    Saint Petersburg, Leningrad Region, Vsevolozhsky District, 188663

  • Pokrovskaya City Hospital

    Saint Petersburg, 199106

  • Clinic of Bashkortostan State Medical University

    Ufa, 450081

Other trials in Russia

Spain8 sites

  • Hospital del Mar

    Barcelona, 08003

  • Hospital Vall D Hebron

    Barcelona, 08035

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08041

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28007

  • MD Anderson Cancer Center Madrid

    Madrid, 28033

  • Hospital Universitario Virgen de la Victoria

    Málaga, 29010

  • Hospital Clinico Universitario de Santiago

    Santiago de Compostela, 15706

  • Instituto Valenciano de Oncologia

    Valencia, 46009

Other trials in Spain

Turkey (Türkiye)8 sites

  • Adana Sehir Hastanesi

    Adana, 01370

  • Dr. Abdurrahman Yurtaslan Ankara Onkoloji EAH

    Ankara, 06200

  • Akdeniz Universitesi Tip Fakultesi

    Antalya, 07059

  • Pamukkale Unv. Tip Fak.

    Denizli, 20070

  • Trakya Universitesi Tip Fakultesi

    Edirne, 22030

  • Marmara Universitesi Pendik Arastirma ve Uyg. Hastanesi

    Istanbul, 34899

  • Dokuz Eylul University Faculty of Medicine

    Izmir, 35340

  • Samsun Medical Park Hastanesi

    Samsun, 55200

Other trials in Turkey (Türkiye)

Germany7 sites

  • Universitaetsklinikum Duesseldorf

    Düsseldorf, 40225

  • Universitatsklinikum Hamburg-Eppendorf

    Hamburg, 20246

  • Universitaetsklinikum Jena

    Jena, 07747

  • Universitaetsklinikum Schleswig-Holstein. Campus Luebeck

    Lübeck, Schleswig-Holstein, 23538

  • Universitaetsklinikum Magdeburg A.o.R.

    Magdeburg, 39120

  • Klinikum rechts der Isar der Technischen Universitat

    München, 81675

  • Universitaetsklinikum Tuebingen

    Tübingen, 72076

Other trials in Germany

Israel7 sites

  • Soroka Medical Center

    Beersheba, 8410101

  • Rambam Medical Center

    Haifa, 31096

  • Meir Medical Center

    Kfar Saba, 4428164

  • Rabin Medical Center

    Petah Tikva, 49100

  • Chaim Sheba Medical Center

    Ramat Gan, 52621

  • Sourasky Medical Center

    Tel Aviv, 6423906

  • Assaf Harofeh Medical Center

    Tsrifin, 70300

Other trials in Israel

United Kingdom7 sites

  • Queen Elizabeth Hospital

    Birmingham, B15 2TH

  • Barts Health NHS Trust - St Bartholomew s Hospital

    London, EC1A 7BE

  • Royal Free London NHS Foundation Trust

    London, NW3 2QG

  • Imperial College Healthcare NHS Trust

    London, W6 8RF

  • Plymouth Hospitals NHS Trust

    Plymouth, PL6 8DH

  • Sunderland Royal Hospital

    Sunderland, SR4 7TP

  • Royal Marsden NHS Trust

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Canada6 sites

  • London Health Sciences Centre

    London, Ontario, N6A 4L6

  • CIUSSS - Hopital Maisonneuve- Rosemont

    Montreal, Quebec, H1T 2M4

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

    Montreal, Quebec, H1T 2M4

  • The Ottawa Hospital Cancer Centre

    Ottawa, Ontario, K1H 8L6

  • CHU de Quebec-Universite Laval-Hotel Dieu de Quebec

    Québec, Quebec, G1R 3S1

  • Sunnybrook Research Institute

    Toronto, Ontario, M4N 3M5

Other trials in Canada

Hungary6 sites

  • Orszagos Onkologiai Intezet

    Budapest, 1122

  • Uzsoki Utcai Korhaz

    Budapest, 1145

  • Somogy Megyei Kaposi Mor Oktato Korhaz

    Kaposvár, 7400

  • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz

    Miskolc, 3526

  • Pecsi Tudomanyegyetem AOK

    Pécs, 7624

  • Jasz - Nagykun Szolnok megyei Hetenyi Geza Korhaz - Rendelointezet

    Szolnok, 5004

Other trials in Hungary

Ireland6 sites

  • Cork University Hospital

    Cork

  • Beaumont Hospital

    Dublin, 00009

  • Adelaide & Meath Hospital (Incl NCH)

    Dublin, 00024

  • University College Hospital Galway

    Galway, H91YR71

  • University Hospital Limerick

    Limerick, V94F858

  • Waterford Regional Hospital

    Waterford, X91ER8E

Other trials in Ireland

Italy5 sites

  • Medical Oncology Ospedale San Donato

    Arezzo, 52100

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

    Meldola, 47014

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, 20133

  • Istituto Nazionale Tumori Fondazione Pascale

    Naples, 80131

  • Istituto Oncologico Veneto

    Padova, 35128

Other trials in Italy

Netherlands5 sites

  • Antoni van Leeuwenhoek Ziekenhuis

    Amsterdam, 1066 CX

  • VU University Medical Center

    Amsterdam, 1081 HV

  • Amphia Ziekenhuis

    Breda, 4819 EV

  • Catharina Ziekenhuis

    Eindhoven, 5623 EJ

  • University Medical Center Groningen

    Groningen, 9713 GZ

Other trials in Netherlands

Taiwan5 sites

  • Chang Gung Medical Foundation. Kaohsiung Branch

    Kaohsiung City, 833

  • China Medical University Hospital

    Taichung, 40447

  • National Cheng Kung University Hospital

    Tainan, 704

  • National Taiwan University Hospital

    Taipei, 100

  • Taipei Veterans General Hospital

    Taipei, 11217

Other trials in Taiwan

Australia4 sites

  • Austin Health-Austin Hospital

    Heidelberg, Victoria, 3084

  • Adelaide Cancer Centre

    Kurralta Park, 5037

  • Macquarie University Hospital

    Macquarie Park, 2109

  • Southern Medical Day Care Centre

    Wollongong, New South Wales, 2500

Other trials in Australia

Denmark4 sites

  • Aalborg University Hospital

    Aalborg, 9000

  • Rigshospitalet

    Copenhagen, 2100

  • Herlev Hospital

    Herlev, 2730

  • Sjaellands Universitetshospital Naestved

    Næstved, 4700

Other trials in Denmark

South Korea4 sites

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital Yonsei University Health System

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

About this study

Official title: 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.

Being tested
Pembrolizumab, Epacadostat, Placebo
Keywords
Urothelial carcinoma, programmed cell death protein 1 (PD-1) inhibitor, indoleamine 2,3-dioxygenase (IDO) inhibitor
Medical subject headings
Carcinoma, Transitional Cell, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called MK-3475

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

  • EpacadostatDrug

    Also called INCB024360

    Epacadostat administered orally twice daily.

  • PlaceboDrug

    Matching placebo administered orally twice daily.

Study groups in NCT03374488
Study groupRoleWhat they receive
Pembrolizumab 200 mg + Epacadostat 100 mg BIDExperimentalPembrolizumab + epacadostat
Receives: Drug: Pembrolizumab; Drug: Epacadostat
Pembrolizumab 200 mg + placebo BIDActive comparatorPembrolizumab + placebo
Receives: Drug: Pembrolizumab; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

    Measured: up to 9 weeks +14 days

Secondary outcomes (2)

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

    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.

    Measured: Up to 8 months

  2. Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE

    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.

    Measured: Up to 8 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Dec 2017
  2. Study start22 Dec 2017
  3. Primary completion27 Jul 2018
  4. Study completion23 Jul 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03374488
Sponsor's protocol ID
KEYNOTE-698/ECHO-303
Other IDs
2017-002310-31, 2017
Status last verified
Aug 2025
First submitted
11 Dec 2017
Last updated
22 Aug 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39054485

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab and Epacadostat in people with UC (Urothelial Cancer), run by Incyte Corporation at 135 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 135 sites in United States, France, Japan, Russia, Spain and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo (time frame: up to 9 weeks +14 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03374488, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2025.

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