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

November 18, 2025 updated by: Incyte Corporation

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)

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

89

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris OBrien Lifehouse
      • North Ryde, New South Wales, Australia, 2109
        • Macquarie University Hospital
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Royal Brisbane & Women s Hospital
  • Austria
      • Salzburg, Austria, 5020
        • Landeskrankenhaus Salzburg
      • Vienna, Austria, 1090
        • Allgemeines Krankenhaus der Stadt Wien
  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Juravinski Cancer Center Hamilton Health Sciences
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
      • Québec, Quebec, Canada, G1R 3S1
        • CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
  • Hungary
      • Miskolc, Hungary, 3526
        • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
      • Szolnok, Hungary, 5000
        • Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet
  • Italy
      • Milan, Italy, 20141
        • Istituto Europeo Di Oncologia
      • Rozzano, Italy, 20089
        • IRRCS Instituto Clinico Humanitas
  • Japan
      • Akashi, Japan, 673-8558
        • Hyogo Cancer Center
      • Fukuoka, Japan, 812-8582
        • Kyushu University Hospital
      • Hiroshima, Japan, 734-8551
        • Hiroshima University Hospital
      • Hokkaido, Japan, 060-8648
        • Hokkaido University Hospital
      • Kobe, Japan, 650-0047
        • Kobe City Medical Center General Hospital
      • Saitama, Japan, 362-0806
        • Saitama Cancer Center
      • Sayama, Japan, 589-8511
        • Kindai University Hospital
      • Shizuoka, Japan, 411-8777
        • Shizuoka Cancer Center Hospital and Research Institute
      • Tokyo, Japan, 135-8550
        • The Cancer Institute Hospital Of JFCR
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
        • National Cancer Center Hospital East
    • Ishikawa-ken
      • Kanazawa, Ishikawa-ken, Japan, 920-8641
        • Kanazawa University Hospital
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 241-8515
        • Kanagawa Cancer Center
    • Miyagi
      • Natori-shi, Miyagi, Japan, 981-1293
        • Miyagi Cancer Center
      • Sendai, Miyagi, Japan, 980-8574
        • Tohoku University Hospital
  • Poland
      • Konin, Poland, 62-500
        • Przychodnia Lekarska KOMED
      • Szczecin, Poland, 71-730
        • Zachodniopomorskie Centrum Onkologii
    • Masovian Voivodeship
      • Wieliszew, Masovian Voivodeship, Poland, 05-135
        • Mazowiecki Szpital Onkologiczny
  • Portugal
      • Coimbra, Portugal, 3000-075
        • Inst. Portugues de Oncologia de Coimbra Frencisco Gentil EPE
      • Lisbon, Portugal, 1099-023
        • Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE
      • Lisbon, Portugal, 1649-035
        • Centro Hospitalar Lisboa Norte EPE - Hospital de Santa Maria
      • Porto, Portugal, 4200-072
        • Inst. Portugues de Oncologia de Porto Francisco Gentil EPE
  • South Korea
      • Seoul, South Korea, 03080
        • Seoul National University Hospital
      • Seoul, South Korea, 05505
        • Asan Medical Center
      • Seoul, South Korea, 03722
        • Severance Hospital Yonsei University Health System
  • Spain
      • Badalona, Spain, 08916
        • Hospital Germans Trias i Pujol. ICO de Badalona
      • Barcelona, Spain, 08035
        • Hospital General Universitari Vall d Hebron
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28034
        • Hospital Ramon y Cajal
      • Madrid, Spain, 28981
        • Hospital Infanta Cristina
      • Seville, Spain, 41014
        • Hospital de Nuestra Senora de Valme
      • Zaragoza, Spain, 50009
        • Hospital Clinico Lozano Blesa
  • Taiwan
      • Tainan, Taiwan, 70457
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 10048
        • National Taiwan University Hospital
      • Taoyuan District, Taiwan, 33305
        • Chang Gung Medical Foundation. Linkou
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye), 01370
        • Adana Sehir Hastanesi
      • Ankara, Turkey (Türkiye), 06100
        • Hacettepe Universitesi Tip Fakultesi Hastanesi
      • Edirne, Turkey (Türkiye), 22030
        • Trakya Universitesi Tip Fakultesi
      • Istanbul, Turkey (Türkiye), 34093
        • Istanbul Üniversitesi Onkoloji Enstitüsü
      • Istanbul, Turkey (Türkiye), 34214
        • Medipol Hastanesi
      • Izmir, Turkey (Türkiye), 35040
        • Ege Universitesi Tip Fakultesi Hastanesi
      • Malatya, Turkey (Türkiye), 44280
        • Inonu Universitesi Turgut Ozal Tip Merkezi
  • United Kingdom
      • London, United Kingdom, N18 1QX
        • North Middlesex Hospital
      • London, United Kingdom, NW1 2PG
        • University College London Hospitals (UCLH)
      • London, United Kingdom, SW3 6JJ
        • The Royal Marsden Foundation Trust
      • London, United Kingdom, SW3 6JJ
        • The Royal Marsden Nhs Foundation Trust - Chelsea
      • Taunton, United Kingdom, TA1 5DA
        • Musgrove Park Hospital
  • United States
    • California
      • Anaheim, California, United States, 19026
        • Pacific Cancer Medical Center
      • Sacramento, California, United States, 95817
        • UC Davis Comprehensive Cancer Center
      • Santa Rosa, California, United States, 95403
        • St. Joseph Heritage Healthcare
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale Cancer Center
    • Georgia
      • Douglasville, Georgia, United States, 30134
        • Northwest Georgia Oncology Centers Pc
    • Kansas
      • Westwood, Kansas, United States, 66205
        • U of Kansas Cancer Center
    • Kentucky
      • Louisville, Kentucky, United States, 40223
        • Baptist Health
    • Montana
      • Billings, Montana, United States, 59102
        • St. Vincent Healthcare Cancer Ctr
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • New Mexico Cancer Care Alliance
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74146
        • Oklahoma Cancer Specialists and Research
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Portland Med Center
    • Utah
      • Salt Lake City, Utah, United States, 19026
        • Huntsman Cancer Institute Univ of Utah
    • Washington
      • Seattle, Washington, United States, 98101
        • Viginia Mason Med Ctr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pembrolizumab
Drug: Pembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
Other Names:
  • MK-3475
Experimental: Pembrolizumab + Epacadostat
Drug: Pembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
Other Names:
  • MK-3475
Drug: Epacadostat
Epacadostat administered orally twice daily.
Other Names:
  • INCB024360
Active Comparator: EXTREME
EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil.
Drug: Cetuximab
Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week.
Drug: Cisplatin
Cisplatin administered intravenously every 3 weeks for
Drug: Carboplatin
Carboplatin administered intravenously every 3 weeks for
Drug: 5-Fluorouracil
5-Fluorouracil administered intravenously every 3 weeks for

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen
Time Frame: Minimum Week 9

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs)
Time Frame: Up to 14 months

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
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs
Time Frame: Up to 14 months

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Incyte Corporation

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Mark Jones, MD, Incyte Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2017

Primary Completion (Actual)

July 19, 2018

Study Completion (Actual)

October 30, 2025

Study Registration Dates

First Submitted

November 27, 2017

First Submitted That Met QC Criteria

November 27, 2017

First Posted (Actual)

November 30, 2017

Study Record Updates

Last Update Posted (Estimated)

December 3, 2025

Last Update Submitted That Met QC Criteria

November 18, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KEYNOTE-669/ECHO 304
  • 2017-001338-24 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Head and Neck Cancer

Clinical Trials on Pembrolizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ukraine

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe