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AzTrials

Lung CancerPhase 2NCT03322540

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

A Phase 2 study testing Pembrolizumab and Epacadostat in people with Lung Cancer, run by Incyte Corporation at 101 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Cancer
What is being tested?
Pembrolizumab and Epacadostat
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
154 participants
Where
101 sitesin 18 countries
Study dates
15 Dec 2017to 9 Nov 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • 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.

Who cannot join

  • 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.
Show all 10Show fewer
  • 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.

Trial locations and contacts

101 sites in 18 countries.

101 sites in 18 countries

Japan17 sites

  • National Hospital Organization Kyushu Cancer Center

    Fukuoka, 811-1395

  • Kyushu University Hospital

    Fukuoka, 812-8582

  • Kansai Medical University Hospital

    Hirakata, Osaka, 573-1191

  • Kanazawa University Hospital

    Kanazawa, Ishikawa-ken, 920-8641

  • Kurume University Hospital

    Kurume, Fukuoka, 830-0011

  • National Hospital Organization Shikoku Cancer Center

    Matsuyama, Ehime, 791-0280

  • Shizuoka Cancer Center

    Nagaizumi-chō, Shizuoka, 411-8777

  • National Hospital Organization Nagoya Medical Center

    Nagoya, Aichi-ken, 460-0001

  • Niigata Cancer Center Hospital

    Niigata, 951-8566

  • Okayama University Hospital

    Okayama, 700-8558

  • Kindai University Hospital

    Sayama, Osaka, 589-8511

  • Sendai Kousei Hospital

    Sendai, Miyagi, 980-0873

  • National Cancer Center Hospital

    Tokyo, 104-0045

  • Nippon Medical School Hospital

    Tokyo, 113-8603

  • The Cancer Institute Hospital of JFCR

    Tokyo, 135-8550

  • Wakayama Medical University Hospital

    Wakayama, 641-8509

  • Kanagawa Cancer Center

    Yokohama, Kanagawa, 241-8515

Other trials in Japan

United States15 sites

  • Pacific Cancer Medical Center, Inc.

    Anaheim, California, 92801

  • Anne Arundel Health System Research Institute

    Annapolis, Maryland, 21401

  • Texas Oncology-South Austin

    Austin, Texas, 78745

  • Weinberg Cancer Institute at Franklin Square

    Baltimore, Maryland, 21237

  • Tennessee Oncology, PLLC/The Sarah Cannon Research Institute

    Chattanooga, Tennessee, 37404

  • Minnesota Oncology Hematology, PA

    Coon Rapids, Minnesota, 55433

  • Florida Cancer Specialists (South Region)

    Fort Myers, Florida, 33916

  • Tennessee Oncology, PLLC/The Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Southeastern Regional Medical Center, Inc.

    Newnan, Georgia, 30265

  • Nebraska Cancer Specialists

    Omaha, Nebraska, 68130

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15224

  • Maryland Oncology Hematology, P.A.

    Rockville, Maryland, 20850

  • Florida Cancer Specialists (North Region)

    St. Petersburg, Florida, 33705

  • Innovative Clinical Research Institute

    Whittier, California, 90603

  • UMass Memorial Medical Center

    Worcester, Massachusetts, 01655

Other trials in United States

Ukraine9 sites

  • Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC

    Dnipropetrovsk, 49102

  • Grigoriev Institute for medical Radiology NAMS of Ukraine

    Kharkiv, 61024

  • PP PPC Acinus Medical and Diagnostic Centre

    Kirovohrad, 25001

  • MI Kryviy Rih Center of Dnipropetrovsk Regional Council

    Kryvyi Rih, Dnipropetrovsk Oblast, 50048

  • Kyiv City Clinical Oncological Center

    Kyiv, 03115

  • Dobryi Prognoz

    Kyiv, 03126

  • Volyn Regional Oncological Dispensary

    Lutsk, 43018

  • MI Odessa Regional Oncological Centre

    Odesa, 65055

  • Zaporizhzhya Regional Clinical Oncology Center

    Zaporizhzhya, 69040

Other trials in Ukraine

Poland8 sites

  • Centrum Onkologii im. Prof. Franciszka Lukaszczyka

    Bydgoszcz, 85-796

  • Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie

    Gliwice, 44-101

  • Swietokrzyskie Centrum Onkologii SPZOZ

    Kielce, 25-734

  • Swietokrzyskie Centrum Onkologii SPZOZ

    Kielce, Świętokrzyskie Voivodeship, 25-734

  • Przychodnia Lekarska Komed

    Konin, 62-500

  • Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc

    Olsztyn, 10-357

  • Wojewodzki Szpital im. Zofii z Zamoyskich Tarnowskiej w Tarnobrzegu

    Tarnobrzeg, 39-400

  • Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie

    Warsaw, 02-781

Other trials in Poland

Spain7 sites

  • Hospital General de Alicante

    Alicante, 03010

  • Hospital del Mar

    Barcelona, 8003

  • Hospital Clinico San Carlos

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario Virgen Macarena

    Seville, 41009

  • Hospital Clinico de Valencia

    Valencia, 46010

  • Hospital Alvaro Cunqueiro

    Vigo, Pontevedra, 36312

Other trials in Spain

Russia6 sites

  • Belgorod Regional Oncology Dispensary

    Belgorod, 308010

  • Central Clinical Hospital with polyclinic

    Moscow, 121359

  • Moscow Research Oncology Institute named after P.A. Hertsen

    Moscow, 125284

  • SBHI Leningrad Regional Clinical Hospital

    Saint Petersburg, 194291

  • SBHI Samara Regional Clinical Oncology Dispensary

    Samara, 443031

  • Republican Clinical Oncology Dispensary of Republic of Bashkortostan

    Ufa, 450054

Other trials in Russia

Canada5 sites

  • William Osler Health System

    Brampton, Ontario, L6R 3J7

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Cancer Centre of Southeastern Ontario at Kingston General Hospital

    Kingston, Ontario, K7L 2V7

  • Moncton Hospital - Horizon Health Network

    Moncton, New Brunswick, E1C 6Z8

  • Sault Area Hospital

    Sault Ste. Marie, Ontario, P6B 0A8

Other trials in Canada

Israel5 sites

  • Soroka Medical Center

    Beersheba, 8457108

  • Rambam Medical Center

    Haifa, 31096

  • Meir Medical Center

    Kfar Saba, 4428164

  • Rabin Medical Center

    Petah Tikva, 4941492

  • Chaim Sheba Medical Center

    Ramat Gan, 52621

Other trials in Israel

Malaysia5 sites

  • University Malaya Medical Centre

    Kuala Lumpur, 59100

  • Pantai Hospital Kuala Lumpur

    Kuala Lumpur

  • Hospital Tengku Ampuan Afzan

    Kuantan, Pahang, 25100

  • Sarawak General Hospital

    Kuching

  • Institut Kanser Negara - National Cancer Institute

    Putrajaya, Kuala Lumpur, 62250

Other trials in Malaysia

Switzerland5 sites

  • Oncological Institute of Southern Switzerland

    Bellinzona, 6500

  • Inselspital Universitatsspital Bern

    Bern, 3010

  • Hopitaux Universitaires de Geneve HUG.

    Geneva, 1211

  • Kantonsspital Winterthur

    Winterthur, 8401

  • Universitaetsspital Zuerich

    Zurich, 8091

Other trials in Switzerland

Turkey (Türkiye)5 sites

  • Basken Uni. Adana Dr.Turgut Noyan Uygulama ve Arastirma Merkezi

    Adana, 01120

  • Ankara University Medical Faculty

    Ankara, 06100

  • Akdeniz Universitesi Tip Fakultesi

    Antalya, 07059

  • Erciyes Universitesi Tip Fakultesi

    Kayseri, 38039

  • Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi

    Konya, 42080

Other trials in Turkey (Türkiye)

Denmark3 sites

  • Rigshospitalet

    Copenhagen, 2100

  • Regionshospitalet Herning

    Herning, 7400

  • Odense Universitetshospital

    Odense, 5000

Other trials in Denmark

South Korea3 sites

  • Chungbuk National University Hospital

    Cheongju-si, North Chungcheong, 28644

  • Gacheon University Gil Medical Center

    Incheon, 21565

  • Seoul National University Bundang Hospital

    Seongnam-si, Gyeonggi-do, 13620

Other trials in South Korea

Australia2 sites

  • Austin Health-Austin Hospital

    Heidelberg, Victoria, 3084

  • St John of God Murdoch Medical Clinic

    Murdoch, Western Australia, 6150

Other trials in Australia

Ireland2 sites

  • St Vincents University Hospital

    Dublin, Dublin 4

  • Galway University Hospital

    Galway, Connacht, H91 YR71

Other trials in Ireland

Italy2 sites

  • IRCCS A.O.U. San Martino - IST

    Genova, 16132

  • Policlinico Universitario Agostino Gemelli

    Roma, 00168

Other trials in Italy

Estonia1 site

  • SA Tartu Ulikooli Kliinikum

    Tartu, 51014

Other trials in Estonia

United Kingdom1 site

  • Leeds Teaching Hospital NHS Trust. St. James University Hospital

    Leeds, LS9 7TF

Other trials in United Kingdom

About this study

Official title: 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).

Conditions
Lung Cancer
Being tested
Pembrolizumab, Epacadostat, Placebo
Keywords
non-small cell lung cancer, programmed cell death 1 (PD-1) inhibitor, indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitor
Medical subject headings
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, 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.

  • PlaceboDrug

    Matching placebo administered orally twice daily.

Study groups in NCT03322540
Study groupRoleWhat they receive
Pembrolizumab + EpacadostatExperimentalParticipants 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.
Receives: Drug: Pembrolizumab; Drug: Epacadostat
Pembrolizumab + PlaceboActive comparatorParticipants 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.
Receives: Drug: Pembrolizumab; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR) of Pembrolizumab Plus Epacadostat Versus Pembrolizumab Plus Placebo

    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).

    Measured: Up to approximately 6 months

Secondary outcomes (5)

  1. Progression-free Survival (PFS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo

    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.

    Measured: Up to approximately 36 months

  2. Overall Survival (OS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo

    OS is defined as the time from randomization to death due to any cause.

    Measured: Up to approximately 36 months

  3. Duration of Response (DOR) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo

    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.

    Measured: Up to approximately 36 months

  4. Number of Participants With 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 37 months

  5. Number of Participants Who Discontinued Study Drug 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 37 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2017
  2. Study start15 Dec 2017
  3. Primary completion10 Jan 2019
  4. Study completion9 Nov 2020

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
154 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03322540
Sponsor's protocol ID
KEYNOTE-654-05/ECHO-305-05
Other IDs
2017-001841-28, 2017
Status last verified
Aug 2025
First submitted
24 Oct 2017
Last updated
22 Aug 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Tokito T, Kolesnik O, Sorensen J, Artac M, Quintela ML, Lee JS, Hussein M, Pless M, Paz-Ares L, Leopold L, Daniel J, Munteanu M, Samkari A, Xu L, Butts C. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab as first-line treatment for metastatic non-small cell lung cancer with high levels of programmed death-ligand 1: a randomized, double-blind phase 2 study. BMC Cancer. 2024 Jul 25;23(Suppl 1):1251. doi: 10.1186/s12885-023-11203-8.

    PubMed 39054476

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Epacadostat in people with Lung Cancer, run by Incyte Corporation at 101 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 101 sites in Japan, United States, Ukraine, Poland, Spain and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) of Pembrolizumab Plus Epacadostat Versus Pembrolizumab Plus Placebo (time frame: Up to approximately 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03322540, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2025.

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