Evidence map›Paper›PMID 39054467›Full record

Trial reportBMC cancer2024

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.

Byoung Chul Cho, Irene Braña, Beatriz Cirauqui, Sercan Aksoy, Felix Couture, Ruey-Long Hong, Wilson H Miller, Manuel Chaves-Conde, Margarida Teixeira, Lance Leopold and 4 more

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in BMC cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03358472 (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), which is not on this map. Cited by 17 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03358472 phase3completednot on this map

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)

TypeinterventionalSponsorIncyte CorporationRan2017 to 2025Enrolled89ConditionsHead and Neck CancerArmsPembrolizumab, Epacadostat, Cetuximab, Cisplatin, Carboplatin
3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Trial
  4. Phase I Evaluation of Patients with Newly Diagnosed Glioblastoma Treated with Radiation, Nivolumab, and IDO1 Enzyme Inhibitor BMS-986205.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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  9. Immunity and Beyond: Emerging Roles of Monocytes and Macrophages in Cancer.Advances in experimental medicine and biology · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Byoung Chul ChoDivision of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seoul, 03722, Republic of Korea. cbc1971@yuhs.ac.ORCID http://orcid.org/0000-0002-5562-270X
Irene BrañaMedical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, 08035, Spain.
Beatriz CirauquiOncology Department, Catalan Institut of Oncology (ICO) Badalona, Crta Canyet sn, Barcelona, 08916, Spain.
Sercan AksoyHacettepe University Cancer Institute, Hacettepe Mh., Ankara, 06100, Turkey.
Felix CoutureCHU de Québec - Hôtel-Dieu de Québec, 11 Cote du Palais, Quebec City, QC, G1R 2J6, Canada.
Ruey-Long HongNational Taiwan University Hospital, No.1, Changde St., Zhongzheng District, Taipei, 100, Taiwan.
Wilson H MillerJewish General Hospital and McGill University, 3755 Cote St., Montreal, H3S 1Z1, Canada.
Manuel Chaves-CondeHospital de Nuestra Senora de Valme, Ctra Cadiz sn, Seville, 41014, Spain.
Margarida TeixeiraInstituto Português de Oncologia de Coimbra Francisco Gentil EPE, Avenida Bissaya Barreto 98, Coimbra, 3000-075, Portugal.
Lance LeopoldIncyte Corporation, Wilmington, DE, 19803, USA.
Mihaela MunteanuIncyte Corporation, Wilmington, DE, 19803, USA.
Joy Yang GeMerck & Co., Inc., P.O. Box 2000, 126 East Lincoln Ave., Rahway, NJ, 07065, USA.
Ramona F SwabyMerck & Co., Inc., P.O. Box 2000, 126 East Lincoln Ave., Rahway, NJ, 07065, USA.
Brett G M HughesRoyal Brisbane and Women's Hospital and University of Queensland, Butterfield Street, Ground Floor, Building 34, Brisbane, QLD, 4029, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAdvanced head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, and new treatment options are needed. Combining immunotherapies with differing mechanisms of action may enhance clinical benefits compared with single-agent immunotherapy. Epacadostat, an indoleamine 2,3 dioxygenase 1 inhibitor, plus pembrolizumab, a PD-1 inhibitor, showed promising activity in advanced HNSCC in the phase 1/2 KEYNOTE-037/ECHO-202 trial.

methodsKEYNOTE-669/ECHO-304 is a randomized, open-label, phase 3 study evaluating the efficacy and safety of pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen (cetuximab with a platinum [carboplatin or cisplatin] and 5-fluorouracil) in recurrent/metastatic (R/M) HNSCC. Participants had no prior systemic therapy for R/M HNSCC and were randomly assigned (2:1:2) to pembrolizumab 200 mg intravenously every 3 weeks plus epacadostat 100 mg orally twice daily, pembrolizumab monotherapy, or EXTREME. The primary endpoint was objective response rate (ORR; investigator assessment). Secondary endpoints were safety and tolerability. Change in serum kynurenine was an exploratory endpoint. Study enrollment was discontinued early as a strategic decision on May 2, 2018, and response assessment was discontinued after first on-study imaging assessment at week 9. Data cut-off was January 17, 2019.

resultsBetween December 1, 2017, and May 2, 2018, 89 patients were randomly allocated to pembrolizumab plus epacadostat (n = 35), pembrolizumab monotherapy (n = 19), or EXTREME (n = 35). ORR (95% CI) was 31% (17%-49%) for pembrolizumab plus epacadostat, 21% (6%-46%) for pembrolizumab monotherapy, and 34% (19%-52%) for EXTREME. Treatment-related adverse events (TRAEs) occurred in 82% (n = 28) of patients receiving pembrolizumab plus epacadostat, 63% (n = 12) receiving pembrolizumab monotherapy, and 100% (n = 34) receiving EXTREME. Grade 3-4 TRAEs occurred in 24% (n = 8) of patients receiving pembrolizumab plus epacadostat, 16% (n = 3) receiving pembrolizumab monotherapy, and 82% (n = 28) receiving EXTREME. No deaths occurred due to AEs. Pembrolizumab plus epacadostat treatment reduced kynurenine levels but not to that of healthy subjects.

conclusionsPembrolizumab plus epacadostat and pembrolizumab monotherapy provided a similar response rate to EXTREME and demonstrated a manageable safety profile in patients with R/M HNSCC.

trial registrationNCT03358472. Date of trial registration: November 30, 2017.

Indexed as

Antibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsHead and Neck NeoplasmsKynurenineNeoplasm Recurrence, LocalSquamous Cell Carcinoma of Head and NeckAdultAgedFemaleHumansMaleMiddle AgedOximesSulfonamidesAntibodies, Monoclonal, HumanizedepacadostatKynurenineOximespembrolizumabSulfonamidesCetuximabEXTREMEHead and neck squamous cell carcinomaImmunotherapyPD-1Pembrolizumab

Identifiers

PMID39054467
PMCPMC11270762

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.