Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care in mRCC (KEYNOTE-679/ECHO-302)

Renal Cell Carcinoma (RCC) Clinical Trial

Official title:

A Randomized, Open-Label, Phase 3 Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care (Sunitinib or Pazopanib) as First-Line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC) (KEYNOTE-679/ECHO-302)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03260894
• Other study ID #: KEYNOTE-679/ECHO-302
• Secondary ID: 2017-002259-26
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 7, 2017
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• 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 plus epacadostat compared to sunitinib or pazopanib in participants with locally advanced/metastatic renal cell carcinoma (mRCC) with a clear cell component who have not received prior systemic therapy for their mRCC.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 129
• Est. completion date: December 31, 2024
• Est. primary completion date: August 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologic confirmation of locally advanced or metastatic RCC with a clear-cell component with or without sarcomatoid features.

• Must not have received any prior systemic therapy for their mRCC.

• Measurable disease based on RECIST v1.1.

• Archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion as required.

• Karnofsky performance status = 70%.

• Adequate organ function per protocol-defined criteria.

Exclusion Criteria:

• Use of protocol-defined prior/concomitant therapy.

• Currently receiving or has received an investigational treatment as part of a study of an investigational agent or has used an investigational device within 4 weeks before randomization.

• History of severe hypersensitivity reaction to study treatments or their excipients.

• Active autoimmune disease that has required systemic treatment in past 2 years.

• Known additional malignancy that has progressed or has required active treatment in the last 3 years.

• Known active central nervous system metastases and/or carcinomatous meningitis.

• History of (noninfectious) pneumonitis that required steroids or current pneumonitis.

• History or presence of an abnormal electrocardiogram that, in the investigator's opinion, is clinically meaningful.

• Significant cardiac event within 12 months before Cycle 1 Day 1.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma (RCC)

Intervention

Drug:
• Pembrolizumab
Pembrolizumab 200 mg administered intravenously every 3 weeks.
• Epacadostat
Epacadostat 100 mg administered orally twice daily.
• Sunitinib
Sunitinib 50 mg administered orally once daily; 4 weeks on, 2 weeks off for 6-wk cycle.
• Pazopanib
Pazopanib 800 mg administered orally once daily.

Locations

Country	Name	City	State
Australia	Canberra Hospital	Garran	Australian Capital Territory
Australia	Cabrini Health	Malvern	Victoria
Australia	Fiona Stanley Hospital	Murdoch
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Brazil	Fundacao Pio XII - Hospital de Cancer de Barretos	Barretos	Sao Paulo
Brazil	Centro Avancado de Tratamento Oncologico - CENANTRON -	Belo Horizonte
Brazil	Centro de pesquisa Porto Alegre	Porto Alegre	Florianopolis
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre
Brazil	Hospital Sao Jose	São Paulo	Sao Paulo
Brazil	Instituto do Cancer de Sao Paulo - ICESP	São Paulo	Sao Paulo
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Kingston Health Sciences Centre - KGH Site	Kingston	Ontario
Canada	Jewish General Hospital	Montréal	Quebec
Canada	CHU de Quebec-Universite Laval-Hotel Dieu de Quebec	Quebec
Canada	Sunnybrook Health Sciences, Odette Cancer Centre	Toronto	Ontario
Canada	CIUSSS de la Mauricie-et-du-Centre-du-Quebec	Trois-Rivières	Quebec
Chile	Clinica Alemana de Osorno	Osorno	Region De Los Lagos
Chile	Fundacion Arturo Lopez Perez FALP	Santiago
Chile	Pontificia Universidad Catolica de Chile	Santiago
Chile	Hospital Clinico Vina del Mar	Vina del Mar
France	CHU Besancon - Hopital Jean Minjoz	Besançon
France	Hopital Saint Andre	Bordeaux
France	Centre Francois Baclesse	Caen
France	Hopital Prive Toulon Hyeres Sainte Marguerite	Hyeres
France	Centre Antoine Lacassagne	Nice	Cedex 2
France	Hopital Europeen Georges Pompidou	Paris
France	Hospices Civils de Lyon Centre Hospitalier Lyon Sud	Pierre Benite
France	CHU de Strasbourg - Nouvel Hopital Civil	Strasbourg
France	Clinique Sainte Anne	Strasbourg
France	Institut Gustave Roussy	Villejuif
Germany	Helios Klinikum Berlin Buch	Berlin
Germany	Universitaetsklinikum der Technischen Universitaet Dresden	Dresden
Germany	Universitaetsklinikum Essen	Essen
Germany	Universitaetsklinikum Frankfurt	Frankfurt am Main
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitaetsklinikum Jena	Jena
Germany	Universitaetsklinikum Magdeburg. Klinik fuer Urologie	Magdeburg
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Hungary	Orszagos Onkologiai Intezet	Budapest	Pest
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz	Kaposvar
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz	Miskolc
Hungary	Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet	Szolnok
Hungary	Markusovszky Egyetemi Oktatokorhaz	Szombathely
Hungary	Zala Megyei Szent Rafael Korhaz	Zalaegerszeg	Pozva
Ireland	Adelaide & Meath Hospital	Dublin
Ireland	University Hospital Waterford	Waterford
Italy	Medical Oncology Ospedale San Donato	Arezzo
Italy	Azienda Ospedaliera-Spedali Civili	Brescia
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	A.O. Cardarelli	Napoli
Italy	Policlinico San Matteo	Pavia
Italy	Azienda Ospedaliera San Camillo Forlanini	Roma
Japan	Akita University Hospital	Akita
Japan	Kyushu University Hospital	Fukuoka
Japan	Saitama Medical University International Medical Center	Hidaka	Saitama
Japan	Nara Medical University Hospital	Kashihara	Nara
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Niigata University Medical & Dental Hospital	Niigata
Japan	Kindai University Hospital	Osakasayama	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Sapporo Medical University Hospital	Sapporo	Hokkaido
Japan	Keio University Hospital	Tokyo
Japan	Nippon Medical School Hospital	Tokyo
Japan	Toranomon Hospital	Tokyo
Japan	Yamaguchi University Hospital	Ube	Yamaguchi
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun	Jeollanam Do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
New Zealand	Auckland City Hospital	Auckland	Grafton
Norway	Helse Bergen HF Haukeland sykehus	Bergen
Norway	Sykehuset Oestfold	Gralum
Norway	Sorlandet sykehus HF	Kristiansand
Norway	Akershus University Hospital	Lørenskog
Norway	Oslo universitetssykehus	Oslo
Norway	Universitetssykehuset i Nord Norge. Kreftavdelingen	Tromsø
Norway	St Olavs Hospital	Trondheim
Russian Federation	Ivanovo regional oncology dispensary	Ivanovo
Russian Federation	Central Clinical Hospital with outpatient Clinic	Moscow
Russian Federation	National Medical Research Radiology Centre	Moscow
Russian Federation	Russian Scientific Center of Roentgenoradiology	Moscow
Russian Federation	Leningrad Regional Oncology Dispensary	Saint Petersburg	Leningrad Region, Vsevolozhsky District
Russian Federation	Republican Clinical Oncology Dispensary of Republic of Bashkortostan	Ufa
Spain	Hospital del Mar	Barcelona
Spain	Hospital Germans Trias i Pujol	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Parc Tauli	Sabadell	Barcelona
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela
Spain	Instituto Valenciano de Oncologia	Valencia
Taiwan	Chang Gung Med 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	Baskent Universitesi Adana Dr. Turgut Noyan Uygulama ve Arastirma Merkezi	Adana
Turkey	Ankara Numune Education and Research Hospital	Ankara
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Istanbul Medeniyet Universitesi Goztepe EAH	Istanbul
Turkey	Istanbul Universitesi Onkoloji Enstitusu	Istanbul
Turkey	Ege Universitesi Tip Fakultesi	Izmir
Turkey	Namik Kemal Universitesi Tip Fakultesi	Tekirdag
Ukraine	Dnipropetrovsk City Multidiscipline Clinical Hosp. 4 of DRC	Dnipropetrovs'k
Ukraine	Dnipropetrovsk Regional Hospital n.a. I.I. Mechnikov	Dnipropetrovs'k
Ukraine	MI Precarpathian Clinical Oncology Center	Ivano-Frankivs'k
Ukraine	MI Kryviy Rih Center of Dnipropetrovsk Regional Council	Kryvyi Rih	Dnipropetrovsk Region
Ukraine	RMI Sumy Regional Clinical Oncology Dispensary	Sumy
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Beatson Institute of Cancer Research	Glasgow
United Kingdom	Barts Health NHS Trust - St Bartholomew s Hospital	London
United Kingdom	The Royal Marsden Foundation Trust	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	The Royal Marsden NHS Foundation Trust.	Sutton	Surrey
United States	New York Oncology Hematology P.C	Albany	New York
United States	Northside Hospital	Atlanta	Georgia
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Tennessee Erlanger Oncology & Hematology	Chattanooga	Tennessee
United States	Rush University Medical Center	Chicago	Illinois
United States	Atlanta Cancer Care - Conyers	Conyers	Georgia
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	The West Clinic, P.C.	Germantown	Tennessee
United States	Southeast Nebraska Hematology & Oncology Consultants, P.C.	Lincoln	Nebraska
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Northwest Georgia Oncology Centers Pc	Marietta	Georgia
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	UC Irvine Comprehensive Cancer Center/Chao Family Comprehensive Cancer Center	Orange	California
United States	Woodlands Medical Specialists, PA	Pensacola	Florida
United States	Oncology & Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care	Roanoke	Virginia
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Pinnacle Oncology Hematology	Scottsdale	Arizona
United States	Scottsdale Healthcare	Scottsdale	Arizona
United States	US Oncology and Research	The Woodlands	Texas
United States	Arizona Oncology Associates PC- HOPE	Tucson	Arizona
United States	Shenandoah Oncology, P.C.	Winchester	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Incyte Corporation	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Chile,  France,  Germany,  Hungary,  Ireland,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Norway,  Russian Federation,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) of Pembrolizumab + Epacadostat Versus Standard of Care (SOC)	ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination.	Minimum up to 6 months
Secondary	Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the 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.	Data reported from start of study to data cutoff 28-Feb-2019, up to 15 months.
Secondary	Safety and Tolerability of Pembrolizumab + Epacadostat Versus SOC as Measured by the Number of Participants Discontinuing Study Drug Due to 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.	Data reported from start of study to data cutoff 28-Feb-2019, up to 15 months.