MedPath

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.
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.

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

🇺🇸

Orange, California, United States

Yale Cancer Center

🇺🇸

New Haven, Connecticut, United States

University of Tennessee Medical Center Knoxville

🇺🇸

Knoxville, Tennessee, United States

GU Research Network-Urology Cancer Center

🇺🇸

Omaha, Nebraska, United States

Quincy Medical Group

🇺🇸

Quincy, Illinois, United States

Macquarie University Hospital

🇦🇺

Macquarie Park, Australia

Hopital de Jolimont

🇧🇪

Haine-Saint-Paul, Belgium

Sunnybrook Health Science Centre

🇨🇦

Toronto, Ontario, Canada

Universitair Ziekenhuis Gent

🇧🇪

Gent, Belgium

Universitaetsklinikum Tuebingen

🇩🇪

Tuebingen, Germany

CHU de Besancon

🇫🇷

Besançon, France

Moncton Hospital - Horizon Health Network

🇨🇦

Moncton, New Brunswick, Canada

Calvary Mater Newcastle

🇦🇺

Waratah, New South Wales, Australia

CHU de Quebec - Hotel-Dieu de Quebec

🇨🇦

Québec, Quebec, Canada

Universitaetsklinikum Schleswig-Holstein. Campus Luebeck

🇩🇪

Luebeck, Schleswig Holstein, Germany

Institut Bergonie

🇫🇷

Bordeaux, France

Cork University Hospital

🇮🇪

Cork, Ireland

Tennessee Oncology, PLLC/The Sarah Cannon Research Institute

🇺🇸

Chattanooga, Tennessee, United States

Austin Health-Austin Hospital

🇦🇺

Heidelberg, Victoria, Australia

Adelaide Cancer Centre

🇦🇺

Kurralta Park, Australia

Centre Jean Perrin

🇫🇷

Clermont-Ferrand, France

CHU de Strasbourg - Nouvel Hopital Civil

🇫🇷

Strasbourg, France

Adelaide & Meath Hospital (Incl NCH)

🇮🇪

Dublin, Ireland

University College Hospital Galway

🇮🇪

Galway, Ireland

C.H.U. de Tours - Hopital Bretonneau

🇫🇷

Tours, France

Kliniken Essen Mitte

🇩🇪

Essen, Germany

Klinikum rechts der Isar der Technischen Universitat

🇩🇪

Muenchen, Germany

Istituto Tumori Giovanni Paolo II

🇮🇹

Bari, Italy

Rambam Health Care Campus

🇮🇱

Haifa, Israel

Nagoya University Hospital

🇯🇵

Nagoya, Aichi, Japan

University Hospital Waterford

🇮🇪

Waterford, Ireland

Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego

🇵🇱

Katowice, Poland

Urologica Praktyka Lekarska Adam Marcheluk

🇵🇱

Siedlce, Poland

China Medical University Hospital

🇨🇳

Taichung, Taiwan

VU University Medical Center

🇳🇱

Amsterdam, Netherlands

Catharina Ziekenhuis

🇳🇱

Eindhoven, Netherlands

Krankenhaus der Barmherzigen Brueder Trier

🇩🇪

Trier, Germany

Ryazan Regional Clinical Oncology Dispensary

🇷🇺

Ryazan, Russian Federation

Rabin Medical Center

🇮🇱

Petach-Tikwa, Israel

Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

Europejskie Centrum Zdrowia Otwock

🇵🇱

Otwock, Poland

Istituto Nazionale dei Tumori

🇮🇹

Milan, Italy

Medical Hospital, Tokyo Medical And Dental University

🇯🇵

Tokyo, Japan

Soroka Medical Center

🇮🇱

Be'er Sheva, Israel

Universitaetsklinikum Magdeburg A.o.R.

🇩🇪

Magdeburg, Germany

Chaim Sheba Medical Center

🇮🇱

Ramat Gan, Israel

Ivanovo Regional Oncology Dispensary

🇷🇺

Ivanovo, Russian Federation

Antoni van Leeuwenhoek Ziekenhuis

🇳🇱

Amsterdam, Netherlands

Meir Medical Center

🇮🇱

Kfar Saba, Israel

University Medical Center Groningen

🇳🇱

Groningen, Netherlands

Istituto Nazionale Tumori IRCCS Fondazione Pascale

🇮🇹

Napoli, Italy

Hospital Teresa Herrera - Chuac

🇪🇸

A Coruña, Spain

Pokrovskaya City Hospital

🇷🇺

Saint Petersburg, Russian Federation

Hospital Infanta Cristina

🇪🇸

Badajoz, Spain

Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej

🇵🇱

Jelenia Góra, Poland

GLOBE Badania Kliniczne Oddzial we Wroclawiu

🇵🇱

Komorowice, Poland

Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie

🇵🇱

Szczecin, Poland

Severance Hospital Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

Russian Scientific Center of Roentgenoradiology

🇷🇺

Moscow, Russian Federation

Chang Gung Medical Foundation - Kaohsiung

🇨🇳

Kaohsiung, Taiwan

MI Odessa Regional Oncological Centre

🇺🇦

Odesa, Ukraine

Erasmus MC

🇳🇱

Rotterdam, Netherlands

ICO L Hospitalet

🇪🇸

Hospitalet de Llobregat, Spain

Tokushima University Hospital

🇯🇵

Tokushima, Japan

National Medical Research Radiological Centre

🇷🇺

Moscow, Russian Federation

Hospital Virgen del Rocio

🇪🇸

Sevilla, Spain

Hospital Universitario Lucus Augusti

🇪🇸

Lugo, Spain

Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC

🇺🇦

Dnipropetrovsk, Ukraine

Magodent Szpital Elblaska

🇵🇱

Warszawa, Poland

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Abramson Cancer Center of the University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Kharkiv Regional Clinical Oncology Center

🇺🇦

Kharkiv, Ukraine

RMI Sumy Regional Clinical Oncology Dispensary

🇺🇦

Sumy, Ukraine

GZA Sint Augustinus

🇧🇪

Wilrijk, Belgium

Institut Jules Bordet

🇧🇪

Bruxelles, Belgium

Grand Hopital de Charleroi - Site Notre Dame - Oncology

🇧🇪

Charleroi, Belgium

AZ Maria Middelares Gent

🇧🇪

Gent, Belgium

AZ Nikolaas

🇧🇪

Sint-Niklaas, Belgium

Comprehensive Cancer Centers of Nevada

🇺🇸

Las Vegas, Nevada, United States

Sarah Cannon Research Institute

🇺🇸

Nashville, Tennessee, United States

Tennessee Oncology Nashville

🇺🇸

Nashville, Tennessee, United States

Texas Oncology-Memorial City

🇺🇸

Houston, Texas, United States

Centre d Oncologie de Gentilly

🇫🇷

Nancy, France

Institut de Cancerologie de l Ouest Site Paul Papin

🇫🇷

Angers, France

Centre Hospitalier Lyon Sud

🇫🇷

Pierre-Bénite, France

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

🇨🇦

Montreal, Quebec, Canada

Kindai University Hospital

🇯🇵

Osakasayama, Osaka, Japan

The Cancer Institute Hospital of JFCR

🇯🇵

Tokyo, Japan

Yamaguchi University Hospital

🇯🇵

Ube, Yamaguchi, Japan

Arizona Oncology Associates PC- HOPE

🇺🇸

Tucson, Arizona, United States

Woodlands Medical Specialists, PA

🇺🇸

Pensacola, Florida, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

🇺🇸

New York, New York, United States

Cancer Centre of Southeastern Ontario at Kingston General Hospital

🇨🇦

Kingston, Ontario, Canada

Institut Jean Godinot

🇫🇷

Reims, France

Universitaetsklinikum Duesseldorf

🇩🇪

Duesseldorf, Germany

Institut Gustave Roussy

🇫🇷

Villejuif, France

Universitatsklinikum Hamburg-Eppendorf

🇩🇪

Hamburg, Germany

University Hospital Limerick

🇮🇪

Limerick, Ireland

Assaf Harofeh Medical Center

🇮🇱

Zerifin, Israel

Medical Oncology Ospedale San Donato

🇮🇹

Arezzo, Italy

Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST

🇮🇹

Meldola, Italy

Istituto Oncologico Veneto

🇮🇹

Padova, Italy

University of Tsukuba Hospital

🇯🇵

Tsukuba, Ibaraki, Japan

Amphia Ziekenhuis

🇳🇱

Breda, Brabant, Netherlands

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Szpital Sw. Elzbiety Mokotowskie Centrum Medyczne

🇵🇱

Warszawa, Poland

Leningrad Regional Oncology Dispensary

🇷🇺

Saint Petersburg, Leningrad Region, Vsevolozhsky District, Russian Federation

Taipei Veterans General Hospital

🇨🇳

Taipei, Beitou, Taiwan

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

🇺🇦

Dnipropetrovsk, Ukraine

Kyiv City Clinical Oncology Center

🇺🇦

Kyiv, Ukraine

Royal Marsden NHS Trust

🇬🇧

Sutton, Surrey, United Kingdom

Imperial College Healthcare NHS Trust

🇬🇧

London, United Kingdom

Barts Health NHS Trust - St Bartholomew's Hospital

🇬🇧

London, United Kingdom

Plymouth Hospitals NHS Trust

🇬🇧

Plymouth, United Kingdom

The Beatson West of Scotland Cancer Centre

🇬🇧

Glasgow, United Kingdom

Sunderland Royal Hospital

🇬🇧

Sunderland, United Kingdom

Levine Cancer Institute

🇺🇸

Charlotte, North Carolina, United States

Fox Chase Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Willamette Valley Cancer Institute and Research Center

🇺🇸

Eugene, Oregon, United States

Medical University of South Carolina-Hollings Cancer Center

🇺🇸

Charleston, South Carolina, United States

Vanderbilt-Ingram Cancer Center

🇺🇸

Nashville, Tennessee, United States

Southern Medical Day Care Centre

🇦🇺

Wollongong, New South Wales, Australia

Institut Paoli Calmettes

🇫🇷

Marseille, France

The Ottawa Hospital Cancer Centre

🇨🇦

Ottawa, Ontario, Canada

National Cancer Center Hospital East

🇯🇵

Kashiwa, Chiba, Japan

Hopital Europeen Georges Pompidou

🇫🇷

Paris, France

Institut Claudius Regaud

🇫🇷

Toulouse, France

Consorci Hospitalari Parc Tauli de Sabadell

🇪🇸

Sabadell, Spain

Universitaetsklinikum Jena

🇩🇪

Jena, Germany

Hospital General Universitari Vall d Hebron

🇪🇸

Barcelona, Spain

Nara Medical University Hospital

🇯🇵

Kashihara, Nara, Japan

N.N. Blokhin NMRCO

🇷🇺

Moscow, Russian Federation

Chungnam National University Hospital

🇰🇷

Daejeon, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Clinic of Bashkortostan State Medical University

🇷🇺

Ufa, Russian Federation

Xarxa Assistencial Universitaria Manresa

🇪🇸

Manresa, Spain

Beskidzkie Centrum Onkologii im. Jana Pawla II

🇵🇱

Bielsko-Biala, Poland

National Cheng Kung University Hospital

🇨🇳

Tainan, Taiwan

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

University of Washington

🇺🇸

Seattle, Washington, United States

Royal Free London NHS Foundation Trust

🇬🇧

London, United Kingdom

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