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

Phase 3
Completed
Conditions
UC (Urothelial Cancer)
Interventions
Registration Number
NCT03361865
Lead Sponsor
Incyte Corporation
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
93
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.
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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.
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Pembrolizumab 200 mg + epacadostat 100 mg BIDEpacadostatPembrolizumab + epacadostat
Pembrolizumab 200 mg + epacadostat 100 mg BIDPembrolizumabPembrolizumab + epacadostat
Pembrolizumab 200 mg + placebo BIDPlaceboPembrolizumab + placebo
Pembrolizumab 200 mg + placebo BIDPembrolizumabPembrolizumab + placebo
Primary Outcome Measures
NameTimeMethod
Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + PlaceboWeek 9

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.

Secondary Outcome Measures
NameTimeMethod
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs)Up to approximately 25 months

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.

Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AEUp to approximately 25 months

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.

Trial Locations

Locations (143)

University of California Irvine Medical Center

๐Ÿ‡บ๐Ÿ‡ธ

Orange, California, United States

Yale Cancer Center

๐Ÿ‡บ๐Ÿ‡ธ

New Haven, Connecticut, United States

University of Tennessee Medical Center Knoxville

๐Ÿ‡บ๐Ÿ‡ธ

Knoxville, Tennessee, United States

GU Research Network-Urology Cancer Center

๐Ÿ‡บ๐Ÿ‡ธ

Omaha, Nebraska, United States

Quincy Medical Group

๐Ÿ‡บ๐Ÿ‡ธ

Quincy, Illinois, United States

Macquarie University Hospital

๐Ÿ‡ฆ๐Ÿ‡บ

Macquarie Park, Australia

Hopital de Jolimont

๐Ÿ‡ง๐Ÿ‡ช

Haine-Saint-Paul, Belgium

Sunnybrook Health Science Centre

๐Ÿ‡จ๐Ÿ‡ฆ

Toronto, Ontario, Canada

Universitair Ziekenhuis Gent

๐Ÿ‡ง๐Ÿ‡ช

Gent, Belgium

Universitaetsklinikum Tuebingen

๐Ÿ‡ฉ๐Ÿ‡ช

Tuebingen, Germany

CHU de Besancon

๐Ÿ‡ซ๐Ÿ‡ท

Besanรงon, France

Moncton Hospital - Horizon Health Network

๐Ÿ‡จ๐Ÿ‡ฆ

Moncton, New Brunswick, Canada

Calvary Mater Newcastle

๐Ÿ‡ฆ๐Ÿ‡บ

Waratah, New South Wales, Australia

CHU de Quebec - Hotel-Dieu de Quebec

๐Ÿ‡จ๐Ÿ‡ฆ

Quรฉbec, Quebec, Canada

Universitaetsklinikum Schleswig-Holstein. Campus Luebeck

๐Ÿ‡ฉ๐Ÿ‡ช

Luebeck, Schleswig Holstein, Germany

Institut Bergonie

๐Ÿ‡ซ๐Ÿ‡ท

Bordeaux, France

Cork University Hospital

๐Ÿ‡ฎ๐Ÿ‡ช

Cork, Ireland

Tennessee Oncology, PLLC/The Sarah Cannon Research Institute

๐Ÿ‡บ๐Ÿ‡ธ

Chattanooga, Tennessee, United States

Austin Health-Austin Hospital

๐Ÿ‡ฆ๐Ÿ‡บ

Heidelberg, Victoria, Australia

Adelaide Cancer Centre

๐Ÿ‡ฆ๐Ÿ‡บ

Kurralta Park, Australia

Centre Jean Perrin

๐Ÿ‡ซ๐Ÿ‡ท

Clermont-Ferrand, France

CHU de Strasbourg - Nouvel Hopital Civil

๐Ÿ‡ซ๐Ÿ‡ท

Strasbourg, France

Adelaide & Meath Hospital (Incl NCH)

๐Ÿ‡ฎ๐Ÿ‡ช

Dublin, Ireland

University College Hospital Galway

๐Ÿ‡ฎ๐Ÿ‡ช

Galway, Ireland

C.H.U. de Tours - Hopital Bretonneau

๐Ÿ‡ซ๐Ÿ‡ท

Tours, France

Kliniken Essen Mitte

๐Ÿ‡ฉ๐Ÿ‡ช

Essen, Germany

Klinikum rechts der Isar der Technischen Universitat

๐Ÿ‡ฉ๐Ÿ‡ช

Muenchen, Germany

Istituto Tumori Giovanni Paolo II

๐Ÿ‡ฎ๐Ÿ‡น

Bari, Italy

Rambam Health Care Campus

๐Ÿ‡ฎ๐Ÿ‡ฑ

Haifa, Israel

Nagoya University Hospital

๐Ÿ‡ฏ๐Ÿ‡ต

Nagoya, Aichi, Japan

University Hospital Waterford

๐Ÿ‡ฎ๐Ÿ‡ช

Waterford, Ireland

Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego

๐Ÿ‡ต๐Ÿ‡ฑ

Katowice, Poland

Urologica Praktyka Lekarska Adam Marcheluk

๐Ÿ‡ต๐Ÿ‡ฑ

Siedlce, Poland

China Medical University Hospital

๐Ÿ‡จ๐Ÿ‡ณ

Taichung, Taiwan

VU University Medical Center

๐Ÿ‡ณ๐Ÿ‡ฑ

Amsterdam, Netherlands

Catharina Ziekenhuis

๐Ÿ‡ณ๐Ÿ‡ฑ

Eindhoven, Netherlands

Krankenhaus der Barmherzigen Brueder Trier

๐Ÿ‡ฉ๐Ÿ‡ช

Trier, Germany

Ryazan Regional Clinical Oncology Dispensary

๐Ÿ‡ท๐Ÿ‡บ

Ryazan, Russian Federation

Rabin Medical Center

๐Ÿ‡ฎ๐Ÿ‡ฑ

Petach-Tikwa, Israel

Sourasky Medical Center

๐Ÿ‡ฎ๐Ÿ‡ฑ

Tel Aviv, Israel

Europejskie Centrum Zdrowia Otwock

๐Ÿ‡ต๐Ÿ‡ฑ

Otwock, Poland

Istituto Nazionale dei Tumori

๐Ÿ‡ฎ๐Ÿ‡น

Milan, Italy

Medical Hospital, Tokyo Medical And Dental University

๐Ÿ‡ฏ๐Ÿ‡ต

Tokyo, Japan

Soroka Medical Center

๐Ÿ‡ฎ๐Ÿ‡ฑ

Be'er Sheva, Israel

Universitaetsklinikum Magdeburg A.o.R.

๐Ÿ‡ฉ๐Ÿ‡ช

Magdeburg, Germany

Chaim Sheba Medical Center

๐Ÿ‡ฎ๐Ÿ‡ฑ

Ramat Gan, Israel

Ivanovo Regional Oncology Dispensary

๐Ÿ‡ท๐Ÿ‡บ

Ivanovo, Russian Federation

Antoni van Leeuwenhoek Ziekenhuis

๐Ÿ‡ณ๐Ÿ‡ฑ

Amsterdam, Netherlands

Meir Medical Center

๐Ÿ‡ฎ๐Ÿ‡ฑ

Kfar Saba, Israel

University Medical Center Groningen

๐Ÿ‡ณ๐Ÿ‡ฑ

Groningen, Netherlands

Istituto Nazionale Tumori IRCCS Fondazione Pascale

๐Ÿ‡ฎ๐Ÿ‡น

Napoli, Italy

Hospital Teresa Herrera - Chuac

๐Ÿ‡ช๐Ÿ‡ธ

A Coruรฑa, Spain

Pokrovskaya City Hospital

๐Ÿ‡ท๐Ÿ‡บ

Saint Petersburg, Russian Federation

Hospital Infanta Cristina

๐Ÿ‡ช๐Ÿ‡ธ

Badajoz, Spain

Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej

๐Ÿ‡ต๐Ÿ‡ฑ

Jelenia Gรณra, Poland

GLOBE Badania Kliniczne Oddzial we Wroclawiu

๐Ÿ‡ต๐Ÿ‡ฑ

Komorowice, Poland

Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie

๐Ÿ‡ต๐Ÿ‡ฑ

Szczecin, Poland

Severance Hospital Yonsei University Health System

๐Ÿ‡ฐ๐Ÿ‡ท

Seoul, Korea, Republic of

Russian Scientific Center of Roentgenoradiology

๐Ÿ‡ท๐Ÿ‡บ

Moscow, Russian Federation

Chang Gung Medical Foundation - Kaohsiung

๐Ÿ‡จ๐Ÿ‡ณ

Kaohsiung, Taiwan

MI Odessa Regional Oncological Centre

๐Ÿ‡บ๐Ÿ‡ฆ

Odesa, Ukraine

Erasmus MC

๐Ÿ‡ณ๐Ÿ‡ฑ

Rotterdam, Netherlands

ICO L Hospitalet

๐Ÿ‡ช๐Ÿ‡ธ

Hospitalet de Llobregat, Spain

Tokushima University Hospital

๐Ÿ‡ฏ๐Ÿ‡ต

Tokushima, Japan

National Medical Research Radiological Centre

๐Ÿ‡ท๐Ÿ‡บ

Moscow, Russian Federation

Hospital Virgen del Rocio

๐Ÿ‡ช๐Ÿ‡ธ

Sevilla, Spain

Hospital Universitario Lucus Augusti

๐Ÿ‡ช๐Ÿ‡ธ

Lugo, Spain

Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC

๐Ÿ‡บ๐Ÿ‡ฆ

Dnipropetrovsk, Ukraine

Magodent Szpital Elblaska

๐Ÿ‡ต๐Ÿ‡ฑ

Warszawa, Poland

Rush University Medical Center

๐Ÿ‡บ๐Ÿ‡ธ

Chicago, Illinois, United States

Massachusetts General Hospital

๐Ÿ‡บ๐Ÿ‡ธ

Boston, Massachusetts, United States

Abramson Cancer Center of the University of Pennsylvania

๐Ÿ‡บ๐Ÿ‡ธ

Philadelphia, Pennsylvania, United States

Kharkiv Regional Clinical Oncology Center

๐Ÿ‡บ๐Ÿ‡ฆ

Kharkiv, Ukraine

RMI Sumy Regional Clinical Oncology Dispensary

๐Ÿ‡บ๐Ÿ‡ฆ

Sumy, Ukraine

GZA Sint Augustinus

๐Ÿ‡ง๐Ÿ‡ช

Wilrijk, Belgium

Institut Jules Bordet

๐Ÿ‡ง๐Ÿ‡ช

Bruxelles, Belgium

Grand Hopital de Charleroi - Site Notre Dame - Oncology

๐Ÿ‡ง๐Ÿ‡ช

Charleroi, Belgium

AZ Maria Middelares Gent

๐Ÿ‡ง๐Ÿ‡ช

Gent, Belgium

AZ Nikolaas

๐Ÿ‡ง๐Ÿ‡ช

Sint-Niklaas, Belgium

Comprehensive Cancer Centers of Nevada

๐Ÿ‡บ๐Ÿ‡ธ

Las Vegas, Nevada, United States

Sarah Cannon Research Institute

๐Ÿ‡บ๐Ÿ‡ธ

Nashville, Tennessee, United States

Tennessee Oncology Nashville

๐Ÿ‡บ๐Ÿ‡ธ

Nashville, Tennessee, United States

Texas Oncology-Memorial City

๐Ÿ‡บ๐Ÿ‡ธ

Houston, Texas, United States

Centre d Oncologie de Gentilly

๐Ÿ‡ซ๐Ÿ‡ท

Nancy, France

Institut de Cancerologie de l Ouest Site Paul Papin

๐Ÿ‡ซ๐Ÿ‡ท

Angers, France

Centre Hospitalier Lyon Sud

๐Ÿ‡ซ๐Ÿ‡ท

Pierre-Bรฉnite, France

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

๐Ÿ‡จ๐Ÿ‡ฆ

Montreal, Quebec, Canada

Kindai University Hospital

๐Ÿ‡ฏ๐Ÿ‡ต

Osakasayama, Osaka, Japan

The Cancer Institute Hospital of JFCR

๐Ÿ‡ฏ๐Ÿ‡ต

Tokyo, Japan

Yamaguchi University Hospital

๐Ÿ‡ฏ๐Ÿ‡ต

Ube, Yamaguchi, Japan

Arizona Oncology Associates PC- HOPE

๐Ÿ‡บ๐Ÿ‡ธ

Tucson, Arizona, United States

Woodlands Medical Specialists, PA

๐Ÿ‡บ๐Ÿ‡ธ

Pensacola, Florida, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

๐Ÿ‡บ๐Ÿ‡ธ

New York, New York, United States

Cancer Centre of Southeastern Ontario at Kingston General Hospital

๐Ÿ‡จ๐Ÿ‡ฆ

Kingston, Ontario, Canada

Institut Jean Godinot

๐Ÿ‡ซ๐Ÿ‡ท

Reims, France

Universitaetsklinikum Duesseldorf

๐Ÿ‡ฉ๐Ÿ‡ช

Duesseldorf, Germany

Institut Gustave Roussy

๐Ÿ‡ซ๐Ÿ‡ท

Villejuif, France

Universitatsklinikum Hamburg-Eppendorf

๐Ÿ‡ฉ๐Ÿ‡ช

Hamburg, Germany

University Hospital Limerick

๐Ÿ‡ฎ๐Ÿ‡ช

Limerick, Ireland

Assaf Harofeh Medical Center

๐Ÿ‡ฎ๐Ÿ‡ฑ

Zerifin, Israel

Medical Oncology Ospedale San Donato

๐Ÿ‡ฎ๐Ÿ‡น

Arezzo, Italy

Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST

๐Ÿ‡ฎ๐Ÿ‡น

Meldola, Italy

Istituto Oncologico Veneto

๐Ÿ‡ฎ๐Ÿ‡น

Padova, Italy

University of Tsukuba Hospital

๐Ÿ‡ฏ๐Ÿ‡ต

Tsukuba, Ibaraki, Japan

Amphia Ziekenhuis

๐Ÿ‡ณ๐Ÿ‡ฑ

Breda, Brabant, Netherlands

Samsung Medical Center

๐Ÿ‡ฐ๐Ÿ‡ท

Seoul, Korea, Republic of

Asan Medical Center

๐Ÿ‡ฐ๐Ÿ‡ท

Seoul, Korea, Republic of

Szpital Sw. Elzbiety Mokotowskie Centrum Medyczne

๐Ÿ‡ต๐Ÿ‡ฑ

Warszawa, Poland

Leningrad Regional Oncology Dispensary

๐Ÿ‡ท๐Ÿ‡บ

Saint Petersburg, Leningrad Region, Vsevolozhsky District, Russian Federation

Taipei Veterans General Hospital

๐Ÿ‡จ๐Ÿ‡ณ

Taipei, Beitou, Taiwan

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

๐Ÿ‡บ๐Ÿ‡ฆ

Dnipropetrovsk, Ukraine

Kyiv City Clinical Oncology Center

๐Ÿ‡บ๐Ÿ‡ฆ

Kyiv, Ukraine

Royal Marsden NHS Trust

๐Ÿ‡ฌ๐Ÿ‡ง

Sutton, Surrey, United Kingdom

Imperial College Healthcare NHS Trust

๐Ÿ‡ฌ๐Ÿ‡ง

London, United Kingdom

Barts Health NHS Trust - St Bartholomew's Hospital

๐Ÿ‡ฌ๐Ÿ‡ง

London, United Kingdom

Plymouth Hospitals NHS Trust

๐Ÿ‡ฌ๐Ÿ‡ง

Plymouth, United Kingdom

The Beatson West of Scotland Cancer Centre

๐Ÿ‡ฌ๐Ÿ‡ง

Glasgow, United Kingdom

Sunderland Royal Hospital

๐Ÿ‡ฌ๐Ÿ‡ง

Sunderland, United Kingdom

Levine Cancer Institute

๐Ÿ‡บ๐Ÿ‡ธ

Charlotte, North Carolina, United States

Fox Chase Cancer Center

๐Ÿ‡บ๐Ÿ‡ธ

Philadelphia, Pennsylvania, United States

Willamette Valley Cancer Institute and Research Center

๐Ÿ‡บ๐Ÿ‡ธ

Eugene, Oregon, United States

Medical University of South Carolina-Hollings Cancer Center

๐Ÿ‡บ๐Ÿ‡ธ

Charleston, South Carolina, United States

Vanderbilt-Ingram Cancer Center

๐Ÿ‡บ๐Ÿ‡ธ

Nashville, Tennessee, United States

Southern Medical Day Care Centre

๐Ÿ‡ฆ๐Ÿ‡บ

Wollongong, New South Wales, Australia

Institut Paoli Calmettes

๐Ÿ‡ซ๐Ÿ‡ท

Marseille, France

The Ottawa Hospital Cancer Centre

๐Ÿ‡จ๐Ÿ‡ฆ

Ottawa, Ontario, Canada

National Cancer Center Hospital East

๐Ÿ‡ฏ๐Ÿ‡ต

Kashiwa, Chiba, Japan

Hopital Europeen Georges Pompidou

๐Ÿ‡ซ๐Ÿ‡ท

Paris, France

Institut Claudius Regaud

๐Ÿ‡ซ๐Ÿ‡ท

Toulouse, France

Consorci Hospitalari Parc Tauli de Sabadell

๐Ÿ‡ช๐Ÿ‡ธ

Sabadell, Spain

Universitaetsklinikum Jena

๐Ÿ‡ฉ๐Ÿ‡ช

Jena, Germany

Hospital General Universitari Vall d Hebron

๐Ÿ‡ช๐Ÿ‡ธ

Barcelona, Spain

Nara Medical University Hospital

๐Ÿ‡ฏ๐Ÿ‡ต

Kashihara, Nara, Japan

N.N. Blokhin NMRCO

๐Ÿ‡ท๐Ÿ‡บ

Moscow, Russian Federation

Chungnam National University Hospital

๐Ÿ‡ฐ๐Ÿ‡ท

Daejeon, Korea, Republic of

Seoul National University Hospital

๐Ÿ‡ฐ๐Ÿ‡ท

Seoul, Korea, Republic of

Clinic of Bashkortostan State Medical University

๐Ÿ‡ท๐Ÿ‡บ

Ufa, Russian Federation

Xarxa Assistencial Universitaria Manresa

๐Ÿ‡ช๐Ÿ‡ธ

Manresa, Spain

Beskidzkie Centrum Onkologii im. Jana Pawla II

๐Ÿ‡ต๐Ÿ‡ฑ

Bielsko-Biala, Poland

National Cheng Kung University Hospital

๐Ÿ‡จ๐Ÿ‡ณ

Tainan, Taiwan

National Taiwan University Hospital

๐Ÿ‡จ๐Ÿ‡ณ

Taipei, Taiwan

University of Washington

๐Ÿ‡บ๐Ÿ‡ธ

Seattle, Washington, United States

Royal Free London NHS Foundation Trust

๐Ÿ‡ฌ๐Ÿ‡ง

London, United Kingdom

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