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

UC (Urothelial Cancer) Clinical Trial

Official title:

A Phase 3 Randomized, Double-Blind Clinical Study 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 (KEYNOTE-698/ECHO-303)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03374488
• Other study ID #: KEYNOTE-698/ECHO-303
• Status: Completed
• Phase: Phase 3
• Start date: December 22, 2017
• Est. completion date: July 23, 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: July 23, 2020
• Est. primary completion date: July 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• UC (Urothelial Cancer)

Intervention

Drug:
• Pembrolizumab
Pembrolizumab administered intravenously Day 1 of each cycle 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	Southern Medical Day Care Centre	Wollongong	New South Wales
Canada	London Health Sciences Centre	London	Ontario
Canada	CIUSSS - Hopital Maisonneuve- Rosemont	Montréal	Quebec
Canada	CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont	Montréal	Quebec
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	CHU de Quebec-Universite Laval-Hotel Dieu de Quebec	Quebec
Canada	CHU de Quebec-Universite Laval-Hotel Dieu de Quebec	Québec	Quebec
Canada	Sunnybrook Research Institute	Toronto	Ontario
Denmark	Aalborg University Hospital	Aalborg
Denmark	Rigshospitalet	Copenhagen
Denmark	Herlev Hospital	Herlev
Denmark	Sjaellands Universitetshospital Naestved	Næstved
France	Institut de Cancerologie de l Ouest Site Paul Papin	Angers
France	Clinique Sainte Catherine	Avignon
France	Centre de Lutte Contre le Cancer Francois Baclesse	Caen
France	Clinique Victor Hugo	Le Mans
France	Centre Oscar Lambret	Lille
France	Centre Leon Berard	Lyon
France	Institut du Cancer de Montpellier	Montpellier
France	Hopital Cochin	Paris
France	Hopital Saint Louis	Paris
France	Institut Jean Godinot	Reims
France	Centre Medico-Chirurgical Foch	Suresnes
France	C.H.U. de Tours - Hopital Bretonneau	Tours
France	Institut Gustave Roussy	Villejuif
Germany	Universitaetsklinikum Duesseldorf	Duesseldorf
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	Universitaetsklinikum Tuebingen	Tuebingen
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Uzsoki Utcai Korhaz	Budapest
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz	Kaposvár
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz	Miskolc
Hungary	Pecsi Tudomanyegyetem AOK	Pécs
Hungary	Jasz - Nagykun Szolnok megyei Hetenyi Geza Korhaz - Rendelointezet	Szolnok
Ireland	Cork University Hospital	Cork
Ireland	Adelaide & Meath Hospital (Incl NCH)	Dublin
Ireland	Beaumont Hospital	Dublin
Ireland	University College Hospital Galway	Galway
Ireland	University Hospital Limerick	Limerick
Ireland	Waterford Regional Hospital	Waterford
Israel	Soroka Medical Center	Be'er Sheva
Israel	Rambam Medical Center	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 Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Istituto Nazionale Tumori 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	Osaka International Cancer Institute	Osaka
Japan	Medical Hospital, Tokyo Medical And Dental University	Tokyo
Japan	Yusen Logistics Co Ltd,. Haneda Logistics Center (MSD DC)	Tokyo
Japan	University of Tsukuba Hospital	Tsukuba	Ibaraki
Japan	Yamaguchi University Hospital	Ube	Yamaguchi
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
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	University Medical Center Groningen	Groningen
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 de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Vall D Hebron	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	MD Anderson Cancer Center Madrid	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Clinico Universitario de Santiago	Santiago De Compostela
Spain	Instituto Valenciano de Oncologia	Valencia
Taiwan	Chang Gung Medical Foundation. Kaohsiung Branch	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
Turkey	Adana Sehir Hastanesi	Adana
Turkey	Dr. Abdurrahman Yurtaslan Ankara Onkoloji EAH	Ankara
Turkey	Akdeniz Universitesi Tip Fakultesi	Antalya
Turkey	Pamukkale Unv. Tip Fak.	Denizli
Turkey	Trakya Universitesi Tip Fakultesi	Edirne
Turkey	Marmara Universitesi Pendik Arastirma ve Uyg. Hastanesi	Istanbul
Turkey	Dokuz Eylul University Faculty of Medicine	Izmir
Turkey	Samsun Medical Park Hastanesi	Samsun
United Kingdom	Queen Elizabeth Hospital	Birmingham
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	University of Michigan Health System	Ann Arbor	Michigan
United States	Northside Hospital, Inc. - GCS/Annex	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Ironwood Cancer & Research Centers	Chandler	Arizona
United States	Medical University of South Carolina-Hollings Cancer Center	Charleston	South Carolina
United States	University of Chicago	Chicago	Illinois
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	US Oncology and Research	Fort Worth	Texas
United States	University of Tennessee Medical Center Knoxville	Knoxville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Smilow Cancer Center at Yale-New Haven	New Haven	Connecticut
United States	NYU Clinical Cancer Center	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	University of California Irvine Medical Center	Orange	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Quincy Medical Group	Quincy	Illinois
United States	VCU Massey Cancer Center	Richmond	Virginia
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	UCLA Hematology Oncology Santa Monica	Santa Monica	California
United States	Oklahoma Cancer Specialists & Research Institute	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Incyte Corporation	Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Denmark,  France,  Germany,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Russian Federation,  Spain,  Taiwan,  Turkey,  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 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	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 8 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 8 months