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

UC (Urothelial Cancer) Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03361865
• Other study ID #: KEYNOTE-672/ECHO-307
• Status: Completed
• Phase: Phase 3
• Start date: December 4, 2017
• Est. completion date: August 4, 2020

Study information

• Verified date: November 2021
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: August 4, 2020
• Est. primary completion date: August 9, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Transitional Cell
• UC (Urothelial Cancer)

Intervention

Drug:
• Pembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
• Epacadostat
Epacadostat administered orally twice daily.
• Placebo
Matching placebo administered orally twice daily.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Incyte Corporation	Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo	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.	Week 9
Secondary	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.	Up to approximately 25 months
Secondary	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.	Up to approximately 25 months