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

NCT03374488 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: KEYNOTE-698/ECHO-3032017-002310-31
• Study Type: interventional
• Target: 84
• Locations: 18 countries
• Sites: 135

Brief 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.

Conditions

UC (Urothelial Cancer)

Keywords

Urothelial carcinoma; programmed cell death protein 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 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.

  up to 9 weeks +14 days

Secondary Outcomes (2)

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

  Up to 8 months

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

  Up to 8 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 Day 1 of each cycle 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-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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (135)

Ironwood Cancer & Research Centers

Chandler, Arizona, 85224, United States

Location

University of California Irvine Medical Center

Orange, California, 92868, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

Location

UCLA Hematology Oncology Santa Monica

Santa Monica, California, 90404, United States

Location

Smilow Cancer Center at Yale-New Haven

New Haven, Connecticut, 06510, United States

Location

Northside Hospital, Inc. - GCS/Annex

Atlanta, Georgia, 30341, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Quincy Medical Group

Quincy, Illinois, 62301, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

NYU Clinical Cancer Center

New York, New York, 10016, United States

Location

Oklahoma Cancer Specialists & Research Institute

Tulsa, Oklahoma, 74146, United States

Location

Oregon Health & Science University

Portland, Oregon, 97210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, 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

University of Tennessee Medical Center Knoxville

Knoxville, Tennessee, 37920, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37203, United States

Location

US Oncology and Research

Fort Worth, Texas, 76177, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

VCU Massey Cancer Center

Richmond, Virginia, 23298, United States

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

London Health Sciences Centre

London, Ontario, N6A 4L6, Canada

Location

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

Location

CIUSSS - Hopital Maisonneuve- Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

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

Montreal, Quebec, H1T 2M4, Canada

Location

CHU de Quebec-Universite Laval-Hotel Dieu de Quebec

Québec, Quebec, G1R 3S1, Canada

Location

Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

Sjaellands Universitetshospital Naestved

Næstved, 4700, Denmark

Location

Institut de Cancerologie de l Ouest Site Paul Papin

Angers, 49055, France

Location

Clinique Sainte Catherine

Avignon, 84918, France

Location

Centre de Lutte Contre le Cancer Francois Baclesse

Caen, 14000, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Institut du Cancer de Montpellier

Montpellier, 34298, France

Location

Hopital Cochin

Paris, 75014, France

Location

Hopital Saint Louis

Paris, 75475, France

Location

Institut Jean Godinot

Reims, 51726, France

Location

Centre Medico-Chirurgical Foch

Suresnes, 92151, 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

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

Universitaetsklinikum Tuebingen

Tübingen, 72076, Germany

Location

Orszagos Onkologiai Intezet

Budapest, 1122, Hungary

Location

Uzsoki Utcai Korhaz

Budapest, 1145, Hungary

Location

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvár, 7400, Hungary

Location

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz

Miskolc, 3526, Hungary

Location

Pecsi Tudomanyegyetem AOK

Pécs, 7624, Hungary

Location

Jasz - Nagykun Szolnok megyei Hetenyi Geza Korhaz - Rendelointezet

Szolnok, 5004, Hungary

Location

Cork University Hospital

Cork, Ireland

Location

Beaumont Hospital

Dublin, 00009, Ireland

Location

Adelaide & Meath Hospital (Incl NCH)

Dublin, 00024, Ireland

Location

University College Hospital Galway

Galway, H91YR71, Ireland

Location

University Hospital Limerick

Limerick, V94F858, Ireland

Location

Waterford Regional Hospital

Waterford, X91ER8E, Ireland

Location

Soroka Medical Center

Beersheba, 8410101, Israel

Location

Rambam Medical Center

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 Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Nazionale Tumori 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

Yamaguchi University Hospital

Ube, Yamaguchi, 755-8505, Japan

Location

Osaka International Cancer Institute

Osaka, 541-8567, Japan

Location

Medical Hospital, Tokyo Medical And Dental University

Tokyo, 113-8519, Japan

Location

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

Tokyo, 144-0042, Japan

Location

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Amphia Ziekenhuis

Breda, 4819 EV, Netherlands

Location

Catharina Ziekenhuis

Eindhoven, 5623 EJ, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

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

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 del Mar

Barcelona, 08003, Spain

Location

Hospital Vall D Hebron

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

MD Anderson Cancer Center Madrid

Madrid, 28033, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Clinico Universitario de Santiago

Santiago de Compostela, 15706, Spain

Location

Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Chang Gung Medical Foundation. Kaohsiung Branch

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

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Adana Sehir Hastanesi

Adana, 01370, Turkey (Türkiye)

Location

Dr. Abdurrahman Yurtaslan Ankara Onkoloji EAH

Ankara, 06200, Turkey (Türkiye)

Location

Akdeniz Universitesi Tip Fakultesi

Antalya, 07059, Turkey (Türkiye)

Location

Pamukkale Unv. Tip Fak.

Denizli, 20070, Turkey (Türkiye)

Location

Trakya Universitesi Tip Fakultesi

Edirne, 22030, Turkey (Türkiye)

Location

Marmara Universitesi Pendik Arastirma ve Uyg. Hastanesi

Istanbul, 34899, Turkey (Türkiye)

Location

Dokuz Eylul University Faculty of Medicine

Izmir, 35340, Turkey (Türkiye)

Location

Samsun Medical Park Hastanesi

Samsun, 55200, Turkey (Türkiye)

Location

Royal Marsden NHS Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, 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)

• 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.

  PMID: 39054485 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; epacadostat

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

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: December 11, 2017
• First Posted: December 15, 2017
• Study Start: December 22, 2017
• Primary Completion: July 27, 2018
• Study Completion: July 23, 2020
• Last Updated: August 22, 2025
• Results First Posted: August 28, 2019

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (24); HU (6); IT (5); DE (7); GB (7); DK (4); IE (6); JP (8); RU (8); CA (6); AU (4); IL (7); KR (4); TW (5); FR (13); NL (5); TU (8); ES (8)