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

NCT03358472 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: KEYNOTE-669/ECHO 3042017-001338-24
• Study Type: interventional
• Target: 89
• Locations: 13 countries
• Sites: 71

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs)

  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

  Up to 14 months

Study Arms (3)

Pembrolizumab + Epacadostat

EXPERIMENTAL

Drug: Pembrolizumab; Drug: Epacadostat

Pembrolizumab

EXPERIMENTAL

Drug: Pembrolizumab

EXTREME

ACTIVE COMPARATOR

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

Drug: Cetuximab; Drug: Cisplatin; Drug: Carboplatin; Drug: 5-Fluorouracil

Interventions

Carboplatin DRUG

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

EXTREME

5-Fluorouracil DRUG

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

EXTREME

Cisplatin DRUG

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

EXTREME

Pembrolizumab DRUG

Pembrolizumab administered intravenously every 3 weeks.

Also known as: MK-3475

Pembrolizumab; Pembrolizumab + Epacadostat

Epacadostat DRUG

Epacadostat administered orally twice daily.

Also known as: INCB024360

Pembrolizumab + Epacadostat

Cetuximab DRUG

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

EXTREME

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Incyte Corporation: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (73)

Pacific Cancer Medical Center

Anaheim, California, 19026, United States

Location

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

St. Joseph Heritage Healthcare

Santa Rosa, California, 95403, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Northwest Georgia Oncology Centers PC

Douglasville, Georgia, 30134, United States

Location

U of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Baptist Health

Louisville, Kentucky, 40223, United States

Location

St. Vincent Healthcare Cancer Ctr

Billings, Montana, 59102, United States

Location

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, 87106, United States

Location

Oklahoma Cancer Specialists and Research

Tulsa, Oklahoma, 74146, United States

Location

Providence Portland Med Center

Portland, Oregon, 97213, United States

Location

Huntsman Cancer Institute Univ of Utah

Salt Lake City, Utah, 19026, United States

Location

Viginia Mason Med Ctr

Seattle, Washington, 98101, United States

Location

Chris OBrien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Macquarie University Hospital

North Ryde, New South Wales, 2109, Australia

Location

Royal Brisbane & Women s Hospital

Herston, Queensland, 4029, Australia

Location

Landeskrankenhaus Salzburg

Salzburg, 5020, Austria

Location

Allgemeines Krankenhaus der Stadt Wien

Vienna, 1090, Austria

Location

Juravinski Cancer Center Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

CHU de Quebec-Universite Laval-Hotel Dieu de Quebec

Québec, Quebec, G1R 3S1, Canada

Location

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz

Miskolc, 3526, Hungary

Location

Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet

Szolnok, 5000, Hungary

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

IRRCS Instituto Clinico Humanitas

Rozzano, 20089, Italy

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Kanagawa Cancer Center

Yokohama, Kanagawa, 241-8515, Japan

Location

Miyagi Cancer Center

Natori-shi, Miyagi, 981-1293, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

Hyogo Cancer Center

Akashi, 673-8558, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Hiroshima University Hospital

Hiroshima, 734-8551, Japan

Location

Hokkaido University Hospital

Hokkaido, 060-8648, Japan

Location

Kobe City Medical Center General Hospital

Kobe, 650-0047, Japan

Location

Saitama Cancer Center

Saitama, 362-0806, Japan

Location

Kindai University Hospital

Sayama, 589-8511, Japan

Location

Shizuoka Cancer Center Hospital and Research Institute

Shizuoka, 411-8777, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

Location

Mazowiecki Szpital Onkologiczny

Wieliszew, Masovian Voivodeship, 05-135, Poland

Location

Przychodnia Lekarska Komed

Konin, 62-500, Poland

Location

Zachodniopomorskie Centrum Onkologii

Szczecin, 71-730, Poland

Location

Inst. Portugues de Oncologia de Coimbra Frencisco Gentil EPE

Coimbra, 3000-075, Portugal

Location

Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE

Lisbon, 1099-023, Portugal

Location

Centro Hospitalar Lisboa Norte EPE - Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

Inst. Portugues de Oncologia de Porto Francisco Gentil EPE

Porto, 4200-072, Portugal

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hospital Germans Trias i Pujol. ICO de Badalona

Badalona, 08916, Spain

Location

Hospital General Universitari Vall d Hebron

Barcelona, 08035, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Infanta Cristina

Madrid, 28981, Spain

Location

Hospital de Nuestra Senora de Valme

Seville, 41014, Spain

Location

Hospital Clinico Lozano Blesa

Zaragoza, 50009, Spain

Location

National Cheng Kung University Hospital

Tainan, 70457, Taiwan

Location

National Taiwan University Hospital

Taipei, 10048, Taiwan

Location

Chang Gung Medical Foundation. Linkou

Taoyuan District, 33305, Taiwan

Location

Adana Sehir Hastanesi

Adana, 01370, Turkey (Türkiye)

Location

Hacettepe Universitesi Tip Fakultesi Hastanesi

Ankara, 06100, Turkey (Türkiye)

Location

Trakya Universitesi Tip Fakultesi

Edirne, 22030, Turkey (Türkiye)

Location

Istanbul Universitesi Onkoloji Enstitusu

Istanbul, 34093, Turkey (Türkiye)

Location

Medipol Hastanesi

Istanbul, 34214, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi Hastanesi

Izmir, 35040, Turkey (Türkiye)

Location

Inonu Universitesi Turgut Ozal Tip Merkezi

Malatya, 44280, Turkey (Türkiye)

Location

North Middlesex Hospital

London, N18 1QX, United Kingdom

Location

University College London Hospitals (UCLH)

London, NW1 2PG, United Kingdom

Location

The Royal Marsden Foundation Trust

London, SW3 6JJ, United Kingdom

Location

The Royal Marsden Nhs Foundation Trust - Chelsea

London, SW3 6JJ, United Kingdom

Location

Musgrove Park Hospital

Taunton, TA1 5DA, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39054467 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; epacadostat; Cetuximab; Cisplatin; Carboplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

855-463-3463

Study Officials

• Mark Jones, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2017
• First Posted: November 30, 2017
• Study Start: December 1, 2017
• Primary Completion: July 19, 2018
• Study Completion: October 30, 2025
• Last Updated: December 3, 2025
• Results First Posted: September 10, 2019

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

HU (2); PL (3); CA (4); PT (4); JP (14); KR (3); US (14); TW (3); IT (2); AU (3); TU (7); GB (5); ES (7)