Pembrolizumab Plus Epacadostat vs Pembrolizumab Plus Placebo in Metastatic Non-Small Cell Lung Cancer (KEYNOTE-654-05/ECHO-305-05)

August 20, 2025 updated by: Incyte Corporation

A Phase 2, Randomized, Double-Blind Study of Pembrolizumab (MK-3475) Plus Epacadostat (INCB024360) Versus Pembrolizumab Plus Placebo as First-Line Treatment in Patients With Metastatic Non-Small Cell Lung Cancer Expressing High Levels of PD-L1

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus epacadostat compared to pembrolizumab plus placebo as first-line treatment in participants with metastatic non-small cell lung cancer (NSCLC) expressing high levels of programmed cell death ligand 1 (PD-L1).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
154

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

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
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health-Austin Hospital
    • Western Australia
      • Murdoch, Western Australia, Australia, 6150
        • St John of God Murdoch Medical Clinic
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6Z8
        • Moncton Hospital - Horizon Health Network
    • Ontario
      • Brampton, Ontario, Canada, L6R 3J7
        • William Osler Health System
      • Kingston, Ontario, Canada, K7L 2V7
        • Cancer Centre of Southeastern Ontario at Kingston General Hospital
      • Sault Ste Marie, Ontario, Canada, P6B 0A8
        • Sault Area Hospital
  • Denmark
      • Copenhagen, Denmark, 2100
        • Rigshospitalet
      • Herning, Denmark, 7400
        • Regionshospitalet Herning
      • Odense, Denmark, 5000
        • Odense Universitetshospital
  • Estonia
      • Tartu, Estonia, 51014
        • SA Tartu Ulikooli Kliinikum
  • Ireland
      • Dublin, Ireland, Dublin 4
        • St Vincents University Hospital
    • Connacht
      • Galway, Connacht, Ireland, H91 YR71
        • Galway University Hospital
  • Israel
      • Beer Sheva, Israel, 8457108
        • Soroka Medical Center
      • Haifa, Israel, 31096
        • Rambam Medical Center
      • Kfar Saba, Israel, 4428164
        • Meir Medical Center
      • Petah Tikva, Israel, 4941492
        • Rabin Medical Center
      • Ramat Gan, Israel, 52621
        • Chaim Sheba Medical Center
  • Italy
      • Genova, Italy, 16132
        • IRCCS A.O.U. San Martino - IST
      • Roma, Italy, 00168
        • Policlinico Universitario Agostino Gemelli
  • Japan
      • Fukuoka, Japan, 811-1395
        • National Hospital Organization Kyushu Cancer Center
      • Fukuoka, Japan, 812-8582
        • Kyushu University Hospital
      • Niigata, Japan, 951-8566
        • Niigata Cancer Center Hospital
      • Okayama, Japan, 700-8558
        • Okayama University Hospital
      • Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
      • Tokyo, Japan, 135-8550
        • The Cancer Institute Hospital of JFCR
      • Tokyo, Japan, 113-8603
        • Nippon Medical School Hospital
      • Wakayama, Japan, 641-8509
        • Wakayama Medical University Hospital
    • Aichi
      • Nagoya, Aichi, Japan, 460-0001
        • National Hospital Organization Nagoya Medical Center
    • Ehime
      • Matsuyama, Ehime, Japan, 791-0280
        • National Hospital Organization Shikoku Cancer Center
    • Fukuoka
      • Kurume, Fukuoka, Japan, 830-0011
        • Kurume University Hospital
    • Ishikawa
      • Kanazawa, Ishikawa, Japan, 920-8641
        • Kanazawa University Hospital
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 241-8515
        • Kanagawa Cancer Center
    • Miyagi
      • Sendai, Miyagi, Japan, 980-0873
        • Sendai Kousei Hospital
    • Osaka
      • Hirakata, Osaka, Japan, 573-1191
        • Kansai Medical University Hospital
      • Osakasayama, Osaka, Japan, 589-8511
        • Kindai University Hospital
    • Shizuoka Prefecture
      • Nagaizumi-chō, Shizuoka Prefecture, Japan, 411-8777
        • Shizuoka Cancer Center
  • Korea, Republic of
      • Incheon, Korea, Republic of, 21565
        • Gacheon University Gil Medical Center
    • Chungcheongbuk Do
      • Cheongju si, Chungcheongbuk Do, Korea, Republic of, 28644
        • Chungbuk National University Hospital
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
        • Seoul National University Bundang Hospital
  • Malaysia
      • Kuala Lumpur, Malaysia, 59100
        • University Malaya Medical Centre
      • Kuala Lumpur, Malaysia
        • Pantai Hospital Kuala Lumpur
      • Kuching, Malaysia
        • Sarawak General Hospital
    • Pahang
      • Kuantan, Pahang, Malaysia, 25100
        • Hospital Tengku Ampuan Afzan
    • Wilayah Persekutuan
      • Putrajaya, Wilayah Persekutuan, Malaysia, 62250
        • Institut Kanser Negara - National Cancer Institute
  • Poland
      • Bydgoszcz, Poland, 85-796
        • Centrum Onkologii im. Prof. Franciszka Lukaszczyka
      • Gliwice, Poland, 44-101
        • Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie
      • Kielce, Poland, 25-734
        • Swietokrzyskie Centrum Onkologii Spzoz
      • Konin, Poland, 62-500
        • Przychodnia Lekarska KOMED
      • Olsztyn, Poland, 10-357
        • Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc
      • Tarnobrzeg, Poland, 39-400
        • Wojewodzki Szpital im. Zofii z Zamoyskich Tarnowskiej w Tarnobrzegu
      • Warszawa, Poland, 02-781
        • Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie
    • Swietokrzyskie
      • Kielce, Swietokrzyskie, Poland, 25-734
        • Swietokrzyskie Centrum Onkologii Spzoz
  • Russian Federation
      • Belgorod, Russian Federation, 308010
        • Belgorod Regional Oncology Dispensary
      • Moscow, Russian Federation, 121359
        • Central Clinical Hospital with polyclinic
      • Moscow, Russian Federation, 125284
        • Moscow Research Oncology Institute named after P.A. Hertsen
      • Saint Petersburg, Russian Federation, 194291
        • SBHI Leningrad Regional Clinical Hospital
      • Samara, Russian Federation, 443031
        • SBHI Samara Regional Clinical Oncology Dispensary
      • Ufa, Russian Federation, 450054
        • Republican Clinical Oncology Dispensary of Republic of Bashkortostan
  • Spain
      • Alicante, Spain, 03010
        • Hospital General de Alicante
      • Barcelona, Spain, 8003
        • Hospital Del Mar
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Sevilla, Spain, 41009
        • Hospital Universitario Virgen Macarena
      • Valencia, Spain, 46010
        • Hospital Clinico de Valencia
    • Pontevedra
      • Vigo, Pontevedra, Spain, 36312
        • Hospital Alvaro Cunqueiro
  • Switzerland
      • Bellinzona, Switzerland, 6500
        • Oncological Institute of Southern Switzerland
      • Bern, Switzerland, 3010
        • INSELSPITAL Universitätsspital Bern
      • Geneva, Switzerland, 1211
        • Hopitaux Universitaires de Geneve HUG.
      • Winterthur, Switzerland, 8401
        • Kantonsspital Winterthur
      • Zuerich, Switzerland, 8091
        • UniversitaetsSpital Zuerich
  • Turkey
      • Adana, Turkey, 01120
        • Basken Uni. Adana Dr.Turgut Noyan Uygulama ve Arastirma Merkezi
      • Ankara, Turkey, 06100
        • Ankara University Medical Faculty
      • Antalya, Turkey, 07059
        • Akdeniz Universitesi Tip Fakultesi
      • Kayseri, Turkey, 38039
        • Erciyes Universitesi Tip Fakultesi
      • Konya, Turkey, 42080
        • Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi
  • Ukraine
      • Dnipropetrovsk, Ukraine, 49102
        • Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC
      • Kharkiv, Ukraine, 61024
        • Grigoriev Institute for Medical Radiology NAMS of Ukraine
      • Kirovohrad, Ukraine, 25001
        • Pp Ppc Acinus Medical and Diagnostic Centre
      • Kyiv, Ukraine, 03115
        • Kyiv City Clinical Oncological Center
      • Kyiv, Ukraine, 03126
        • Dobryi Prognoz
      • Lutsk, Ukraine, 43018
        • Volyn Regional Oncological Dispensary
      • Odesa, Ukraine, 65055
        • MI Odessa Regional Oncological Centre
      • Zaporizhzhya, Ukraine, 69040
        • Zaporizhzhya Regional Clinical Oncology Center
    • Dnipropetrovsk Region
      • Kryvyi Rih, Dnipropetrovsk Region, Ukraine, 50048
        • MI Kryviy Rih Center of Dnipropetrovsk Regional Council
  • United Kingdom
      • Leeds, United Kingdom, LS9 7TF
        • Leeds Teaching Hospital NHS Trust. St. James University Hospital
  • United States
    • California
      • Anaheim, California, United States, 92801
        • Pacific Cancer Medical Center, Inc.
      • Whittier, California, United States, 90603
        • Innovative Clinical Research Institute
    • Florida
      • Fort Myers, Florida, United States, 33916
        • Florida Cancer Specialists (South Region)
      • Saint Petersburg, Florida, United States, 33705
        • Florida Cancer Specialists (North Region)
    • Georgia
      • Newnan, Georgia, United States, 30265
        • Southeastern Regional Medical Center, Inc.
    • Maryland
      • Annapolis, Maryland, United States, 21401
        • Anne Arundel Health System Research Institute
      • Baltimore, Maryland, United States, 21237
        • Weinberg Cancer Institute at Franklin Square
      • Rockville, Maryland, United States, 20850
        • Maryland Oncology Hematology, P.A.
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial Medical Center
    • Minnesota
      • Coon Rapids, Minnesota, United States, 55433
        • Minnesota Oncology Hematology, PA
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Nebraska Cancer Specialists
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Allegheny General Hospital
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Tennessee Oncology, PLLC/The Sarah Cannon Research Institute
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC/The Sarah Cannon Research Institute
    • Texas
      • Austin, Texas, United States, 78745
        • Texas Oncology-South Austin

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of stage IV NSCLC without epidermal growth factor receptor (EGFR)-sensitizing mutation, ROS1 and/or anaplastic lymphoma kinase (ALK) translocation.
  • Measurable disease based on RECIST 1.1.
  • Tumor tissue that demonstrates programmed cell death ligand 1 (PD-L1) expression in ≥ 50% of tumor cells (tumor proportion score [TPS] ≥ 50%) as assessed by immunohistochemistry at a central laboratory.
  • Life expectancy of at least 3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate organ function per protocol-defined criteria.

Exclusion Criteria:

  • Known untreated central nervous system metastases and/or carcinomatous meningitis.
  • History of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
  • Symptomatic ascites or pleural effusion.
  • Known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
  • Active autoimmune disease that has required systemic treatment in past 2 years.
  • Has had an allogeneic tissue/solid organ transplant.
  • Has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority.
  • Has known history of or is positive for active Hepatitis B (HBsAg reactive) or has active Hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.
  • History or presence of an abnormal electrocardiogram (ECG) that, in the Investigator's opinion, is clinically meaningful.
  • Use of protocol-defined prior/concomitant therapy.

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: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Pembrolizumab + Epacadostat
Participants received pembrolizumab 200 mg as an intravenous (IV) infusion, every three weeks (Q3W) starting on Day 1 of each cycle for up to 35 administrations in combination with epacadostat 100 mg orally, twice daily. Epacodostat administration was discontinued after the implementation of protocol amendment 05.
Drug: Pembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
Other Names:
  • MK-3475
Drug: Epacadostat
Epacadostat administered orally twice daily.
Other Names:
  • INCB024360
Active Comparator: Pembrolizumab + Placebo
Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05.
Drug: Pembrolizumab
Pembrolizumab administered intravenously every 3 weeks.
Other Names:
  • MK-3475
Drug: Placebo
Matching placebo administered orally twice daily.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) of Pembrolizumab Plus Epacadostat Versus Pembrolizumab Plus Placebo
Time Frame: Up to approximately 6 months
ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 based on blinded independent central review (BICR).
Up to approximately 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
Time Frame: Up to approximately 36 months
PFS is defined as the time from randomization to the first documented progressive disease per RECIST v1.1 based on BICR or death due to any cause, whichever occurs first.
Up to approximately 36 months
Overall Survival (OS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
Time Frame: Up to approximately 36 months
OS is defined as the time from randomization to death due to any cause.
Up to approximately 36 months
Duration of Response (DOR) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
Time Frame: Up to approximately 36 months
DOR is defined as the time from the earliest date of qualifying response until earliest date of disease progression per RECIST v1.1 or death from any cause, whichever comes first.
Up to approximately 36 months
Number of Participants With Adverse Events (AEs)
Time Frame: Up to 37 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.
Up to 37 months
Number of Participants Who Discontinued Study Drug Due to AEs
Time Frame: Up to 37 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.
Up to 37 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Incyte Corporation

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck Sharp & Dohme LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Lance Leopold, MD, Incyte Corporation

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 15, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 10, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 9, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 24, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 26, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 22, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 20, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KEYNOTE-654-05/ECHO-305-05
  • 2017-001841-28 (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.

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