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

NCT ID: NCT03358472

Last Updated: 2025-12-03

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

89 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-01

Study Completion Date

2025-10-30

Brief Summary

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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).

Detailed Description

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Conditions

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Head and Neck Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pembrolizumab + Epacadostat

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

Pembrolizumab administered intravenously every 3 weeks.

Epacadostat

Intervention Type DRUG

Epacadostat administered orally twice daily.

Pembrolizumab

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

Pembrolizumab administered intravenously every 3 weeks.

EXTREME

EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil.

Group Type ACTIVE_COMPARATOR

Cetuximab

Intervention Type DRUG

Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week.

Cisplatin

Intervention Type DRUG

Cisplatin administered intravenously every 3 weeks for \</= 6 cycles.

Carboplatin

Intervention Type DRUG

Carboplatin administered intravenously every 3 weeks for \</= 6 cycles.

5-Fluorouracil

Intervention Type DRUG

5-Fluorouracil administered intravenously every 3 weeks for \</= 6 cycles.

Interventions

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Pembrolizumab

Pembrolizumab administered intravenously every 3 weeks.

Intervention Type DRUG

Epacadostat

Epacadostat administered orally twice daily.

Intervention Type DRUG

Cetuximab

Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week.

Intervention Type DRUG

Cisplatin

Cisplatin administered intravenously every 3 weeks for \</= 6 cycles.

Intervention Type DRUG

Carboplatin

Carboplatin administered intravenously every 3 weeks for \</= 6 cycles.

Intervention Type DRUG

5-Fluorouracil

5-Fluorouracil administered intravenously every 3 weeks for \</= 6 cycles.

Intervention Type DRUG

Other Intervention Names

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MK-3475 INCB024360

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mark Jones, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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Pacific Cancer Medical Center

Anaheim, California, United States

Site Status

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

St. Joseph Heritage Healthcare

Santa Rosa, California, United States

Site Status

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Northwest Georgia Oncology Centers PC

Douglasville, Georgia, United States

Site Status

U of Kansas Cancer Center

Westwood, Kansas, United States

Site Status

Baptist Health

Louisville, Kentucky, United States

Site Status

St. Vincent Healthcare Cancer Ctr

Billings, Montana, United States

Site Status

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, United States

Site Status

Oklahoma Cancer Specialists and Research

Tulsa, Oklahoma, United States

Site Status

Providence Portland Med Center

Portland, Oregon, United States

Site Status

Huntsman Cancer Institute Univ of Utah

Salt Lake City, Utah, United States

Site Status

Viginia Mason Med Ctr

Seattle, Washington, United States

Site Status

Chris OBrien Lifehouse

Camperdown, New South Wales, Australia

Site Status

Macquarie University Hospital

North Ryde, New South Wales, Australia

Site Status

Royal Brisbane & Women s Hospital

Herston, Queensland, Australia

Site Status

Landeskrankenhaus Salzburg

Salzburg, , Austria

Site Status

Allgemeines Krankenhaus der Stadt Wien

Vienna, , Austria

Site Status

Juravinski Cancer Center Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

CHU de Quebec-Universite Laval-Hotel Dieu de Quebec

Québec, Quebec, Canada

Site Status

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz

Miskolc, , Hungary

Site Status

Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet

Szolnok, , Hungary

Site Status

Istituto Europeo di Oncologia

Milan, , Italy

Site Status

IRRCS Instituto Clinico Humanitas

Rozzano, , Italy

Site Status

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Site Status

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, Japan

Site Status

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Site Status

Miyagi Cancer Center

Natori-shi, Miyagi, Japan

Site Status

Tohoku University Hospital

Sendai, Miyagi, Japan

Site Status

Hyogo Cancer Center

Akashi, , Japan

Site Status

Kyushu University Hospital

Fukuoka, , Japan

Site Status

Hiroshima University Hospital

Hiroshima, , Japan

Site Status

Hokkaido University Hospital

Hokkaido, , Japan

Site Status

Kobe City Medical Center General Hospital

Kobe, , Japan

Site Status

Saitama Cancer Center

Saitama, , Japan

Site Status

Kindai University Hospital

Sayama, , Japan

Site Status

Shizuoka Cancer Center Hospital and Research Institute

Shizuoka, , Japan

Site Status

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

Site Status

Mazowiecki Szpital Onkologiczny

Wieliszew, Masovian Voivodeship, Poland

Site Status

Przychodnia Lekarska Komed

Konin, , Poland

Site Status

Zachodniopomorskie Centrum Onkologii

Szczecin, , Poland

Site Status

Inst. Portugues de Oncologia de Coimbra Frencisco Gentil EPE

Coimbra, , Portugal

Site Status

Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE

Lisbon, , Portugal

Site Status

Centro Hospitalar Lisboa Norte EPE - Hospital de Santa Maria

Lisbon, , Portugal

Site Status

Inst. Portugues de Oncologia de Porto Francisco Gentil EPE

Porto, , Portugal

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Hospital Germans Trias i Pujol. ICO de Badalona

Badalona, , Spain

Site Status

Hospital General Universitari Vall d Hebron

Barcelona, , Spain

Site Status

Hospital Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Infanta Cristina

Madrid, , Spain

Site Status

Hospital de Nuestra Senora de Valme

Seville, , Spain

Site Status

Hospital Clinico Lozano Blesa

Zaragoza, , Spain

Site Status

National Cheng Kung University Hospital

Tainan, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Chang Gung Medical Foundation. Linkou

Taoyuan District, , Taiwan

Site Status

Adana Sehir Hastanesi

Adana, , Turkey (Türkiye)

Site Status

Hacettepe Universitesi Tip Fakultesi Hastanesi

Ankara, , Turkey (Türkiye)

Site Status

Trakya Universitesi Tip Fakultesi

Edirne, , Turkey (Türkiye)

Site Status

Istanbul Universitesi Onkoloji Enstitusu

Istanbul, , Turkey (Türkiye)

Site Status

Medipol Hastanesi

Istanbul, , Turkey (Türkiye)

Site Status

Ege Universitesi Tip Fakultesi Hastanesi

Izmir, , Turkey (Türkiye)

Site Status

Inonu Universitesi Turgut Ozal Tip Merkezi

Malatya, , Turkey (Türkiye)

Site Status

North Middlesex Hospital

London, , United Kingdom

Site Status

University College London Hospitals (UCLH)

London, , United Kingdom

Site Status

The Royal Marsden Foundation Trust

London, , United Kingdom

Site Status

The Royal Marsden Nhs Foundation Trust - Chelsea

London, , United Kingdom

Site Status

Musgrove Park Hospital

Taunton, , United Kingdom

Site Status

Countries

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United States Australia Austria Canada Hungary Italy Japan Poland Portugal South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

References

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Cho BC, Brana I, Cirauqui B, Aksoy S, Couture F, Hong RL, Miller WH Jr, Chaves-Conde M, Teixeira M, Leopold L, Munteanu M, Ge JY, Swaby RF, Hughes BGM. Pembrolizumab plus epacadostat in patients with recurrent/metastatic head and neck squamous cell carcinoma (KEYNOTE-669/ECHO-304): a phase 3, randomized, open-label study. BMC Cancer. 2024 Jul 25;23(Suppl 1):1254. doi: 10.1186/s12885-023-11316-0.

Reference Type DERIVED
PMID: 39054467 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2017-001338-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KEYNOTE-669/ECHO 304

Identifier Type: -

Identifier Source: org_study_id

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