Back to resultsPembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)
Primary Purpose
Head and Neck Cancer
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Pembrolizumab
Epacadostat
Cetuximab
Cisplatin
Carboplatin
5-Fluorouracil
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Cancer focused on measuring Head and neck squamous cell carcinoma, programmed cell death 1 (PD-1) inhibitor, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor
Eligibility Criteria
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).
Sites / Locations
- Pacific Cancer Medical Center
- UC Davis Comprehensive Cancer Center
- St. Joseph Heritage Healthcare
- University of Colorado Cancer Center
- Yale Cancer Center
- Northwest Georgia Oncology Centers PC
- U of Kansas Cancer Center
- Baptist Health
- St. Vincent Healthcare Cancer Ctr
- New Mexico Cancer Care Alliance
- Oklahoma Cancer Specialists and Research
- Providence Portland Med Center
- Huntsman Cancer Institute Univ of Utah
- Viginia Mason Med Ctr
- Chris OBrien Lifehouse
- Macquarie University Hospital
- Royal Brisbane & Women s Hospital
- Landeskrankenhaus Salzburg
- Allgemeines Krankenhaus der Stadt Wien
- Juravinski Cancer Center Hamilton Health Sciences
- Princess Margaret Cancer Centre
- Jewish General Hospital
- CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
- Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
- Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet
- Istituto Europeo di Oncologia
- IRRCS Instituto Clinico Humanitas
- National Cancer Center Hospital East
- Kanazawa University Hospital
- Kanagawa Cancer Center
- Miyagi Cancer Center
- Tohoku University Hospital
- Hyogo Cancer Center
- Kyushu University Hospital
- Hiroshima University Hospital
- Hokkaido University Hospital
- Kobe City Medical Center General Hospital
- Kindai University Hospital
- Saitama Cancer Center
- Shizuoka Cancer Center Hospital and Research Institute
- The Cancer Institute Hospital of JFCR
- Seoul National University Hospital
- Severance Hospital Yonsei University Health System
- Asan Medical Center
- Mazowiecki Szpital Onkologiczny
- Przychodnia Lekarska Komed
- Zachodniopomorskie Centrum Onkologii
- Inst. Portugues de Oncologia de Coimbra Frencisco Gentil EPE
- Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE
- Centro Hospitalar Lisboa Norte EPE - Hospital de Santa Maria
- Inst. Portugues de Oncologia de Porto Francisco Gentil EPE
- Hospital Germans Trias i Pujol. ICO de Badalona
- Hospital General Universitari Vall d Hebron
- Hospital Ramon y Cajal
- Hospital Universitario 12 de Octubre
- Hospital Infanta Cristina
- Hospital de Nuestra Senora de Valme
- Hospital Clinico Lozano Blesa
- National Cheng Kung University Hospital
- National Taiwan University Hospital
- Chang Gung Medical Foundation. Linkou
- Adana Sehir Hastanesi
- Hacettepe Universitesi Tip Fakultesi Hastanesi
- Trakya Universitesi Tip Fakultesi
- Istanbul Universitesi Onkoloji Enstitusu
- Medipol Hastanesi
- Ege Universitesi Tip Fakultesi Hastanesi
- Inonu Universitesi Turgut Ozal Tip Merkezi
- North Middlesex Hospital
- University College London Hospitals (UCLH)
- The Royal Marsden Foundation Trust
- The Royal Marsden Nhs Foundation Trust - Chelsea
- Musgrove Park Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Pembrolizumab + Epacadostat
Pembrolizumab
EXTREME
Arm Description
EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT03358472
First Posted
November 27, 2017
Last Updated
July 31, 2023
Sponsor
Incyte Corporation
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT03358472
Brief Title
Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 1, 2017 (Actual)
Primary Completion Date
July 19, 2018 (Actual)
Study Completion Date
December 27, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
Head and neck squamous cell carcinoma, programmed cell death 1 (PD-1) inhibitor, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
89 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pembrolizumab + Epacadostat
Arm Type
Experimental
Arm Title
Pembrolizumab
Arm Type
Experimental
Arm Title
EXTREME
Arm Type
Active Comparator
Arm Description
EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
MK-3475
Intervention Description
Pembrolizumab administered intravenously every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Epacadostat
Other Intervention Name(s)
INCB024360
Intervention Description
Epacadostat administered orally twice daily.
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Intervention Description
Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Cisplatin administered intravenously every 3 weeks for </= 6 cycles.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin administered intravenously every 3 weeks for </= 6 cycles.
Intervention Type
Drug
Intervention Name(s)
5-Fluorouracil
Intervention Description
5-Fluorouracil administered intravenously every 3 weeks for </= 6 cycles.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen
Description
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.
Time Frame
Minimum Week 9
Secondary Outcome Measure Information:
Title
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs)
Description
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.
Time Frame
Up to 14 months
Title
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs
Description
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.
Time Frame
Up to 14 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Jones, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Pacific Cancer Medical Center
City
Anaheim
State/Province
California
ZIP/Postal Code
19026
Country
United States
Facility Name
UC Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
St. Joseph Heritage Healthcare
City
Santa Rosa
State/Province
California
ZIP/Postal Code
95403
Country
United States
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Northwest Georgia Oncology Centers PC
City
Douglasville
State/Province
Georgia
ZIP/Postal Code
30134
Country
United States
Facility Name
U of Kansas Cancer Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Baptist Health
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40223
Country
United States
Facility Name
St. Vincent Healthcare Cancer Ctr
City
Billings
State/Province
Montana
ZIP/Postal Code
59102
Country
United States
Facility Name
New Mexico Cancer Care Alliance
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
Oklahoma Cancer Specialists and Research
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74146
Country
United States
Facility Name
Providence Portland Med Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
Huntsman Cancer Institute Univ of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
19026
Country
United States
Facility Name
Viginia Mason Med Ctr
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Chris OBrien Lifehouse
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Macquarie University Hospital
City
North Ryde
State/Province
New South Wales
ZIP/Postal Code
2109
Country
Australia
Facility Name
Royal Brisbane & Women s Hospital
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Landeskrankenhaus Salzburg
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Allgemeines Krankenhaus der Stadt Wien
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Juravinski Cancer Center Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
City
Quebec
ZIP/Postal Code
G1R 3S1
Country
Canada
Facility Name
Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
City
Miskolc
ZIP/Postal Code
3526
Country
Hungary
Facility Name
Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet
City
Szolnok
ZIP/Postal Code
5000
Country
Hungary
Facility Name
Istituto Europeo di Oncologia
City
Milano
ZIP/Postal Code
20141
Country
Italy
Facility Name
IRRCS Instituto Clinico Humanitas
City
Rozzano
ZIP/Postal Code
20089
Country
Italy
Facility Name
National Cancer Center Hospital East
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Facility Name
Kanazawa University Hospital
City
Kanazawa
State/Province
Ishikawa
ZIP/Postal Code
920-8641
Country
Japan
Facility Name
Kanagawa Cancer Center
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
241-8515
Country
Japan
Facility Name
Miyagi Cancer Center
City
Natori
State/Province
Miyagi
ZIP/Postal Code
981-1293
Country
Japan
Facility Name
Tohoku University Hospital
City
Sendai
State/Province
Miyagi
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
Hyogo Cancer Center
City
Akashi
ZIP/Postal Code
673-8558
Country
Japan
Facility Name
Kyushu University Hospital
City
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Hiroshima University Hospital
City
Hiroshima
ZIP/Postal Code
734-8551
Country
Japan
Facility Name
Hokkaido University Hospital
City
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Kobe City Medical Center General Hospital
City
Kobe
ZIP/Postal Code
650-0047
Country
Japan
Facility Name
Kindai University Hospital
City
Osakasayama City
ZIP/Postal Code
589-8511
Country
Japan
Facility Name
Saitama Cancer Center
City
Saitama
ZIP/Postal Code
362-0806
Country
Japan
Facility Name
Shizuoka Cancer Center Hospital and Research Institute
City
Shizuoka
ZIP/Postal Code
411-8777
Country
Japan
Facility Name
The Cancer Institute Hospital of JFCR
City
Tokyo
ZIP/Postal Code
135-8550
Country
Japan
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Severance Hospital Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Mazowiecki Szpital Onkologiczny
City
Wieliszew
State/Province
Mazowieckie
ZIP/Postal Code
05-135
Country
Poland
Facility Name
Przychodnia Lekarska Komed
City
Konin
ZIP/Postal Code
62-500
Country
Poland
Facility Name
Zachodniopomorskie Centrum Onkologii
City
Szczecin
ZIP/Postal Code
71-730
Country
Poland
Facility Name
Inst. Portugues de Oncologia de Coimbra Frencisco Gentil EPE
City
Coimbra
ZIP/Postal Code
3000-075
Country
Portugal
Facility Name
Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE
City
Lisboa
ZIP/Postal Code
1099-023
Country
Portugal
Facility Name
Centro Hospitalar Lisboa Norte EPE - Hospital de Santa Maria
City
Lisboa
ZIP/Postal Code
1649-035
Country
Portugal
Facility Name
Inst. Portugues de Oncologia de Porto Francisco Gentil EPE
City
Porto
ZIP/Postal Code
4200-072
Country
Portugal
Facility Name
Hospital Germans Trias i Pujol. ICO de Badalona
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital General Universitari Vall d Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Infanta Cristina
City
Madrid
ZIP/Postal Code
28981
Country
Spain
Facility Name
Hospital de Nuestra Senora de Valme
City
Sevilla
ZIP/Postal Code
41014
Country
Spain
Facility Name
Hospital Clinico Lozano Blesa
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Facility Name
National Cheng Kung University Hospital
City
Tainan
ZIP/Postal Code
70457
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10048
Country
Taiwan
Facility Name
Chang Gung Medical Foundation. Linkou
City
Taoyuan
ZIP/Postal Code
33305
Country
Taiwan
Facility Name
Adana Sehir Hastanesi
City
Adana
ZIP/Postal Code
01370
Country
Turkey
Facility Name
Hacettepe Universitesi Tip Fakultesi Hastanesi
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Trakya Universitesi Tip Fakultesi
City
Edirne
ZIP/Postal Code
22030
Country
Turkey
Facility Name
Istanbul Universitesi Onkoloji Enstitusu
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Medipol Hastanesi
City
Istanbul
ZIP/Postal Code
34214
Country
Turkey
Facility Name
Ege Universitesi Tip Fakultesi Hastanesi
City
Izmir
ZIP/Postal Code
35040
Country
Turkey
Facility Name
Inonu Universitesi Turgut Ozal Tip Merkezi
City
Malatya
ZIP/Postal Code
44280
Country
Turkey
Facility Name
North Middlesex Hospital
City
London
ZIP/Postal Code
N18 1QX
Country
United Kingdom
Facility Name
University College London Hospitals (UCLH)
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Facility Name
The Royal Marsden Foundation Trust
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
The Royal Marsden Nhs Foundation Trust - Chelsea
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
Musgrove Park Hospital
City
Taunton
ZIP/Postal Code
TA1 5DA
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)
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