Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)

Head and Neck Cancer Clinical Trial

Official title:

A Phase 3 Randomized, Open-Label Clinical Study to Evaluate the Efficacy and Safety of Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen as First Line Treatment for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03358472
• Other study ID #: KEYNOTE-669/ECHO 304
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 1, 2017
• Est. completion date: December 27, 2024

Study information

• Verified date: January 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, pembrolizumab monotherapy, and the EXTREME regimen (cetuximab + cisplatin or carboplatin + 5-fluorouracil) as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 89
• Est. completion date: December 27, 2024
• Est. primary completion date: July 19, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Measurable disease based on RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function per protocol-defined criteria.
• Documentation of results from testing of human papilloma virus (HPV) status for oropharyngeal cancer.
• Baseline archival tumor specimen available or willing to undergo a prestudy treatment tumor core or excisional biopsy of a tumor lesion not previously irradiated, to obtain the specimen.

Exclusion Criteria:

• Carcinoma of the nasopharynx, salivary gland, unknown primary origin, or nonsquamous histologies as primary tumors.
• Disease progression within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.
• Use of protocol-defined prior/concomitant therapy.
• 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.
• 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 (defined as hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (defined as HCV RNA [qualitative] is detected).

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Pembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
• Epacadostat
Epacadostat administered orally twice daily.
• Cetuximab
Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week.
• Cisplatin
Cisplatin administered intravenously every 3 weeks for </= 6 cycles.
• Carboplatin
Carboplatin administered intravenously every 3 weeks for </= 6 cycles.
• 5-Fluorouracil
5-Fluorouracil administered intravenously every 3 weeks for </= 6 cycles.

Locations

Country	Name	City	State
Australia	Chris OBrien Lifehouse	Camperdown	New South Wales
Australia	Royal Brisbane & Women s Hospital	Herston	Queensland
Australia	Macquarie University Hospital	North Ryde	New South Wales
Austria	Landeskrankenhaus Salzburg	Salzburg
Austria	Allgemeines Krankenhaus der Stadt Wien	Wien
Canada	Juravinski Cancer Center Hamilton Health Sciences	Hamilton	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Canada	CHU de Quebec-Universite Laval-Hotel Dieu de Quebec	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz	Miskolc
Hungary	Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet	Szolnok
Italy	Istituto Europeo di Oncologia	Milano
Italy	IRRCS Instituto Clinico Humanitas	Rozzano
Japan	Hyogo Cancer Center	Akashi
Japan	Kyushu University Hospital	Fukuoka
Japan	Hiroshima University Hospital	Hiroshima
Japan	Hokkaido University Hospital	Hokkaido
Japan	Kanazawa University Hospital	Kanazawa	Ishikawa
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Kobe City Medical Center General Hospital	Kobe
Japan	Miyagi Cancer Center	Natori	Miyagi
Japan	Kindai University Hospital	Osakasayama City
Japan	Saitama Cancer Center	Saitama
Japan	Tohoku University Hospital	Sendai	Miyagi
Japan	Shizuoka Cancer Center Hospital and Research Institute	Shizuoka
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Kanagawa Cancer Center	Yokohama	Kanagawa
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Poland	Przychodnia Lekarska Komed	Konin
Poland	Zachodniopomorskie Centrum Onkologii	Szczecin
Poland	Mazowiecki Szpital Onkologiczny	Wieliszew	Mazowieckie
Portugal	Inst. Portugues de Oncologia de Coimbra Frencisco Gentil EPE	Coimbra
Portugal	Centro Hospitalar Lisboa Norte EPE - Hospital de Santa Maria	Lisboa
Portugal	Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE	Lisboa
Portugal	Inst. Portugues de Oncologia de Porto Francisco Gentil EPE	Porto
Spain	Hospital Germans Trias i Pujol. ICO de Badalona	Badalona
Spain	Hospital General Universitari Vall d Hebron	Barcelona
Spain	Hospital Infanta Cristina	Madrid
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital de Nuestra Senora de Valme	Sevilla
Spain	Hospital Clinico Lozano Blesa	Zaragoza
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Medical Foundation. Linkou	Taoyuan
Turkey	Adana Sehir Hastanesi	Adana
Turkey	Hacettepe Universitesi Tip Fakultesi Hastanesi	Ankara
Turkey	Trakya Universitesi Tip Fakultesi	Edirne
Turkey	Istanbul Universitesi Onkoloji Enstitusu	Istanbul
Turkey	Medipol Hastanesi	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Hastanesi	Izmir
Turkey	Inonu Universitesi Turgut Ozal Tip Merkezi	Malatya
United Kingdom	North Middlesex Hospital	London
United Kingdom	The Royal Marsden Foundation Trust	London
United Kingdom	The Royal Marsden Nhs Foundation Trust - Chelsea	London
United Kingdom	University College London Hospitals (UCLH)	London
United Kingdom	Musgrove Park Hospital	Taunton
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	Pacific Cancer Medical Center	Anaheim	California
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	St. Vincent Healthcare Cancer Ctr	Billings	Montana
United States	Northwest Georgia Oncology Centers PC	Douglasville	Georgia
United States	Baptist Health	Louisville	Kentucky
United States	Yale Cancer Center	New Haven	Connecticut
United States	Providence Portland Med Center	Portland	Oregon
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Huntsman Cancer Institute Univ of Utah	Salt Lake City	Utah
United States	St. Joseph Heritage Healthcare	Santa Rosa	California
United States	Viginia Mason Med Ctr	Seattle	Washington
United States	Oklahoma Cancer Specialists and Research	Tulsa	Oklahoma
United States	U of Kansas Cancer Center	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Incyte Corporation	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Hungary,  Italy,  Japan,  Korea, Republic of,  Poland,  Portugal,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen	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.; Responses are based on investigator assessments per RECIST 1.1 without confirmation using all available scans.	Minimum Week 9
Secondary	Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen 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.; Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months.	Up to 14 months
Secondary	Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment 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 17 Jan 2019, up to 14 months.	Up to 14 months