Head and Neck CancerPhase 3NCT03358472
Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)
A Phase 3 study testing Pembrolizumab, Epacadostat and Cetuximab in people with Head and Neck Cancer, run by Incyte Corporation at 73 sites in 14 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- Pembrolizumab, Epacadostat and Cetuximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 89 participants
- Where
- 73 sitesin 14 countries
- Study dates
- 1 Dec 2017to 30 Oct 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
73 sites in 14 countries.
73 sites in 14 countries
United States14 sites
New Mexico Cancer Care Alliance
Albuquerque, New Mexico, 87106
Pacific Cancer Medical Center
Anaheim, California, 19026
University of Colorado Cancer Center
Aurora, Colorado, 80045
St. Vincent Healthcare Cancer Ctr
Billings, Montana, 59102
Northwest Georgia Oncology Centers PC
Douglasville, Georgia, 30134
Baptist Health
Louisville, Kentucky, 40223
Yale Cancer Center
New Haven, Connecticut, 06520
Providence Portland Med Center
Portland, Oregon, 97213
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817
Huntsman Cancer Institute Univ of Utah
Salt Lake City, Utah, 19026
St. Joseph Heritage Healthcare
Santa Rosa, California, 95403
Viginia Mason Med Ctr
Seattle, Washington, 98101
Oklahoma Cancer Specialists and Research
Tulsa, Oklahoma, 74146
U of Kansas Cancer Center
Westwood, Kansas, 66205
Japan14 sites
Hyogo Cancer Center
Akashi, 673-8558
Kyushu University Hospital
Fukuoka, 812-8582
Hiroshima University Hospital
Hiroshima, 734-8551
Hokkaido University Hospital
Hokkaido, 060-8648
Kanazawa University Hospital
Kanazawa, Ishikawa-ken, 920-8641
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
Kobe City Medical Center General Hospital
Kobe, 650-0047
Miyagi Cancer Center
Natori-shi, Miyagi, 981-1293
Saitama Cancer Center
Saitama, 362-0806
Kindai University Hospital
Sayama, 589-8511
Tohoku University Hospital
Sendai, Miyagi, 980-8574
Shizuoka Cancer Center Hospital and Research Institute
Shizuoka, 411-8777
The Cancer Institute Hospital of JFCR
Tokyo, 135-8550
Kanagawa Cancer Center
Yokohama, Kanagawa, 241-8515
Spain7 sites
Hospital Germans Trias i Pujol. ICO de Badalona
Badalona, 08916
Hospital General Universitari Vall d Hebron
Barcelona, 08035
Hospital Ramon y Cajal
Madrid, 28034
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Infanta Cristina
Madrid, 28981
Hospital de Nuestra Senora de Valme
Seville, 41014
Hospital Clinico Lozano Blesa
Zaragoza, 50009
Turkey (Türkiye)7 sites
Adana Sehir Hastanesi
Adana, 01370
Hacettepe Universitesi Tip Fakultesi Hastanesi
Ankara, 06100
Trakya Universitesi Tip Fakultesi
Edirne, 22030
Istanbul Universitesi Onkoloji Enstitusu
Istanbul, 34093
Medipol Hastanesi
Istanbul, 34214
Ege Universitesi Tip Fakultesi Hastanesi
Izmir, 35040
Inonu Universitesi Turgut Ozal Tip Merkezi
Malatya, 44280
United Kingdom5 sites
North Middlesex Hospital
London, N18 1QX
University College London Hospitals (UCLH)
London, NW1 2PG
The Royal Marsden Foundation Trust
London, SW3 6JJ
The Royal Marsden Nhs Foundation Trust - Chelsea
London, SW3 6JJ
Musgrove Park Hospital
Taunton, TA1 5DA
Canada4 sites
Juravinski Cancer Center Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2
Jewish General Hospital
Montreal, Quebec, H3T 1E2
CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
Québec, Quebec, G1R 3S1
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
Portugal4 sites
Inst. Portugues de Oncologia de Coimbra Frencisco Gentil EPE
Coimbra, 3000-075
Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE
Lisbon, 1099-023
Centro Hospitalar Lisboa Norte EPE - Hospital de Santa Maria
Lisbon, 1649-035
Inst. Portugues de Oncologia de Porto Francisco Gentil EPE
Porto, 4200-072
Australia3 sites
Chris OBrien Lifehouse
Camperdown, New South Wales, 2050
Royal Brisbane & Women s Hospital
Herston, Queensland, 4029
Macquarie University Hospital
North Ryde, New South Wales, 2109
Poland3 sites
Przychodnia Lekarska Komed
Konin, 62-500
Zachodniopomorskie Centrum Onkologii
Szczecin, 71-730
Mazowiecki Szpital Onkologiczny
Wieliszew, Masovian Voivodeship, 05-135
South Korea3 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Taiwan3 sites
National Cheng Kung University Hospital
Tainan, 70457
National Taiwan University Hospital
Taipei, 10048
Chang Gung Medical Foundation. Linkou
Taoyuan, 33305
Austria2 sites
Landeskrankenhaus Salzburg
Salzburg, 5020
Allgemeines Krankenhaus der Stadt Wien
Vienna, 1090
Hungary2 sites
Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
Miskolc, 3526
Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet
Szolnok, 5000
Italy2 sites
Istituto Europeo di Oncologia
Milan, 20141
IRRCS Instituto Clinico Humanitas
Rozzano, 20089
About this study
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)
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
- Being tested
- Pembrolizumab, Epacadostat, Cetuximab, Cisplatin, Carboplatin
- Keywords
- Head and neck squamous cell carcinoma, programmed cell death 1 (PD-1) inhibitor, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called MK-3475
Pembrolizumab administered intravenously every 3 weeks.
EpacadostatDrug
Also called INCB024360
Epacadostat administered orally twice daily.
CetuximabDrug
Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week.
CisplatinDrug
Cisplatin administered intravenously every 3 weeks for </= 6 cycles.
CarboplatinDrug
Carboplatin administered intravenously every 3 weeks for </= 6 cycles.
5-FluorouracilDrug
5-Fluorouracil administered intravenously every 3 weeks for </= 6 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + Epacadostat | Experimental | Not described Receives: Drug: Pembrolizumab; Drug: Epacadostat |
| Pembrolizumab | Experimental | Not described Receives: Drug: Pembrolizumab |
| EXTREME | Active comparator | EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. Receives: Drug: Cetuximab; Drug: Cisplatin; Drug: Carboplatin; Drug: 5-Fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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.
Measured: up to approximately 8 years
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.
Measured: up to approximately 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2017
- Study start1 Dec 2017
- Primary completion19 Jul 2018
- Study completion30 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Incyte CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- Incyte Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Mark Jones, MD, Study director, Incyte Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03358472
- Sponsor's protocol ID
- KEYNOTE-669/ECHO 304
- Other IDs
- 2017-001338-24, 2017
- Status last verified
- Sep 2026
- First submitted
- 27 Nov 2017
- Last updated
- 29 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39054467