Clinical trial NCT03361865: Pembrolizumab in Combination With Epacadostat or Placebo in Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)
Official title: A Phase 3 Randomized, Double-Blind Trial of Pembrolizumab (MK-3475) in Combination With Epacadostat (INCB024360) or Placebo in Participants With Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: UC (Urothelial Cancer)
Keywords: Urothelial cancer, programmed cell death 1 (PD-1) inhibitor
indoleamine 2,3-dioxygenase (IDO) inhibitor
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-12-05
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
timeFrame: Week 9
Secondary outcomes:
measure: Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to approximately 25 months
measure: Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE
timeFrame: Up to approximately 25 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates PC- HOPE
state: Arizona
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Pensacola
country: United States
facility: Woodlands Medical Specialists, PA
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Quincy
country: United States
facility: Quincy Medical Group
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Omaha
country: United States
facility: GU Research Network-Urology Cancer Center
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina-Hollings Cancer Center
state: South Carolina
city: Chattanooga
country: United States
facility: Tennessee Oncology, PLLC/The Sarah Cannon Research Institute
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee Medical Center Knoxville
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology Nashville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: Texas Oncology-Memorial City
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
state: New South Wales
city: Heidelberg
country: Australia
facility: Austin Health-Austin Hospital
state: Victoria
city: Kurralta Park
country: Australia
facility: Adelaide Cancer Centre
city: Macquarie Park
country: Australia
facility: Macquarie University Hospital
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi - Site Notre Dame - Oncology
city: Gent
country: Belgium
facility: AZ Maria Middelares Gent
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Haine-Saint-Paul
country: Belgium
facility: Hopital de Jolimont
city: Sint-Niklaas
country: Belgium
facility: AZ Nikolaas
city: Wilrijk
country: Belgium
facility: GZA Sint Augustinus
city: Moncton
country: Canada
facility: Moncton Hospital - Horizon Health Network
state: New Brunswick
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont
state: Quebec
city: Québec
country: Canada
facility: CHU de Quebec - Hotel-Dieu de Quebec
state: Quebec
city: Angers
country: France
facility: Institut de Cancerologie de l Ouest Site Paul Papin
city: Besançon
country: France
facility: CHU de Besancon
city: Bordeaux
country: France
facility: Institut Bergonie
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nancy
country: France
facility: Centre d Oncologie de Gentilly
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Reims
country: France
facility: Institut Jean Godinot
city: Strasbourg
country: France
facility: CHU de Strasbourg - Nouvel Hopital Civil
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Tours
country: France
facility: C.H.U. de Tours - Hopital Bretonneau
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein. Campus Luebeck
state: Schleswig Holstein
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Essen
country: Germany
facility: Kliniken Essen Mitte
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Magdeburg
country: Germany
facility: Universitaetsklinikum Magdeburg A.o.R.
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der Technischen Universitat
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Brueder Trier
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Adelaide & Meath Hospital (Incl NCH)
city: Galway
country: Ireland
facility: University College Hospital Galway
city: Limerick
country: Ireland
facility: University Hospital Limerick
city: Waterford
country: Ireland
facility: University Hospital Waterford
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petach-Tikwa
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Zerifin
country: Israel
facility: Assaf Harofeh Medical Center
city: Arezzo
country: Italy
facility: Medical Oncology Ospedale San Donato
city: Bari
country: Italy
facility: Istituto Tumori Giovanni Paolo II
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST
city: Milan
country: Italy
facility: Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital
state: Ibaraki
city: Kashihara
country: Japan
facility: Nara Medical University Hospital
state: Nara
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Ube
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Tokushima
country: Japan
facility: Tokushima University Hospital
city: Tokyo
country: Japan
facility: Medical Hospital, Tokyo Medical And Dental University
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
state: Brabant
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Bielsko-Biala
country: Poland
facility: Beskidzkie Centrum Onkologii im. Jana Pawla II
city: Jelenia Góra
country: Poland
facility: Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej
city: Katowice
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego
city: Komorowice
country: Poland
facility: GLOBE Badania Kliniczne Oddzial we Wroclawiu
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock
city: Siedlce
country: Poland
facility: Urologica Praktyka Lekarska Adam Marcheluk
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie
city: Warszawa
country: Poland
facility: Magodent Szpital Elblaska
city: Warszawa
country: Poland
facility: Szpital Sw. Elzbiety Mokotowskie Centrum Medyczne
city: Saint Petersburg
country: Russian Federation
facility: Leningrad Regional Oncology Dispensary
state: Leningrad Region, Vsevolozhsky District
city: Ivanovo
country: Russian Federation
facility: Ivanovo Regional Oncology Dispensary
city: Moscow
country: Russian Federation
facility: N.N. Blokhin NMRCO
city: Moscow
country: Russian Federation
facility: Russian Scientific Center of Roentgenoradiology
city: Moscow
country: Russian Federation
facility: National Medical Research Radiological Centre
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Oncology Dispensary
city: Saint Petersburg
country: Russian Federation
facility: Pokrovskaya City Hospital
city: Ufa
country: Russian Federation
facility: Clinic of Bashkortostan State Medical University
city: A Coruña
country: Spain
facility: Hospital Teresa Herrera - Chuac
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina
city: Barcelona
country: Spain
facility: Hospital General Universitari Vall d Hebron
city: Hospitalet de Llobregat
country: Spain
facility: ICO L Hospitalet
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Manresa
country: Spain
facility: Xarxa Assistencial Universitaria Manresa
city: Sabadell
country: Spain
facility: Consorci Hospitalari Parc Tauli de Sabadell
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
state: Beitou
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Dnipropetrovsk
country: Ukraine
facility: MI Dnipr Regional Clinical Hospital named after I.I. Mechnikov
city: Dnipropetrovsk
country: Ukraine
facility: Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Oncology Center
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Oncology Center
city: Odesa
country: Ukraine
facility: MI Odessa Regional Oncological Centre
city: Sumy
country: Ukraine
facility: RMI Sumy Regional Clinical Oncology Dispensary
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Trust
state: Surrey
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Barts Health NHS Trust - St Bartholomew's Hospital
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
Study officials:
affiliation: Incyte Corporation
name: Mark Jones, MD
role: STUDY_DIRECTOR
References: