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

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

154

Phase

  • 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 Universitatsspital 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

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
Intervention / Treatment
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

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

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

Incyte Corporation

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • 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)

December 15, 2017

Primary Completion (Actual)

January 10, 2019

Study Completion (Actual)

November 9, 2020

Study Registration Dates

First Submitted

October 24, 2017

First Submitted That Met QC Criteria

October 24, 2017

First Posted (Actual)

October 26, 2017

Study Record Updates

Last Update Posted (Actual)

August 22, 2025

Last Update Submitted That Met QC Criteria

August 20, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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.

Clinical Trials on Lung Cancer

Clinical Trials on Pembrolizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kazakhstan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe