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

NCT ID: NCT03322540

Last Updated: 2025-08-22

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

154 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-15

Study Completion Date

2020-11-09

Brief Summary

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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).

Detailed Description

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Conditions

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Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
With the implementation of Amendment 05 the study is no longer blinded.

Study Groups

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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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

Pembrolizumab administered intravenously every 3 weeks.

Epacadostat

Intervention Type DRUG

Epacadostat administered orally twice daily.

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.

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type DRUG

Pembrolizumab administered intravenously every 3 weeks.

Placebo

Intervention Type DRUG

Matching placebo administered orally twice daily.

Interventions

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Pembrolizumab

Pembrolizumab administered intravenously every 3 weeks.

Intervention Type DRUG

Epacadostat

Epacadostat administered orally twice daily.

Intervention Type DRUG

Placebo

Matching placebo administered orally twice daily.

Intervention Type DRUG

Other Intervention Names

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MK-3475 INCB024360

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lance Leopold, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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Pacific Cancer Medical Center, Inc.

Anaheim, California, United States

Site Status

Innovative Clinical Research Institute

Whittier, California, United States

Site Status

Florida Cancer Specialists (South Region)

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists (North Region)

St. Petersburg, Florida, United States

Site Status

Southeastern Regional Medical Center, Inc.

Newnan, Georgia, United States

Site Status

Anne Arundel Health System Research Institute

Annapolis, Maryland, United States

Site Status

Weinberg Cancer Institute at Franklin Square

Baltimore, Maryland, United States

Site Status

Maryland Oncology Hematology, P.A.

Rockville, Maryland, United States

Site Status

UMass Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Minnesota Oncology Hematology, PA

Coon Rapids, Minnesota, United States

Site Status

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Tennessee Oncology, PLLC/The Sarah Cannon Research Institute

Chattanooga, Tennessee, United States

Site Status

Tennessee Oncology, PLLC/The Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Texas Oncology-South Austin

Austin, Texas, United States

Site Status

Austin Health-Austin Hospital

Heidelberg, Victoria, Australia

Site Status

St John of God Murdoch Medical Clinic

Murdoch, Western Australia, Australia

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

Moncton Hospital - Horizon Health Network

Moncton, New Brunswick, Canada

Site Status

William Osler Health System

Brampton, Ontario, Canada

Site Status

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada

Site Status

Sault Area Hospital

Sault Ste. Marie, Ontario, Canada

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Regionshospitalet Herning

Herning, , Denmark

Site Status

Odense Universitetshospital

Odense, , Denmark

Site Status

SA Tartu Ulikooli Kliinikum

Tartu, , Estonia

Site Status

Galway University Hospital

Galway, Connacht, Ireland

Site Status

St Vincents University Hospital

Dublin, , Ireland

Site Status

Soroka Medical Center

Beersheba, , Israel

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

Meir Medical Center

Kfar Saba, , Israel

Site Status

Rabin Medical Center

Petah Tikva, , Israel

Site Status

Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

IRCCS A.O.U. San Martino - IST

Genova, , Italy

Site Status

Policlinico Universitario Agostino Gemelli

Roma, , Italy

Site Status

National Hospital Organization Nagoya Medical Center

Nagoya, Aichi-ken, Japan

Site Status

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, Japan

Site Status

Kurume University Hospital

Kurume, Fukuoka, Japan

Site Status

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, Japan

Site Status

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Site Status

Sendai Kousei Hospital

Sendai, Miyagi, Japan

Site Status

Kansai Medical University Hospital

Hirakata, Osaka, Japan

Site Status

Kindai University Hospital

Sayama, Osaka, Japan

Site Status

Shizuoka Cancer Center

Nagaizumi-chō, Shizuoka, Japan

Site Status

National Hospital Organization Kyushu Cancer Center

Fukuoka, , Japan

Site Status

Kyushu University Hospital

Fukuoka, , Japan

Site Status

Niigata Cancer Center Hospital

Niigata, , Japan

Site Status

Okayama University Hospital

Okayama, , Japan

Site Status

National Cancer Center Hospital

Tokyo, , Japan

Site Status

Nippon Medical School Hospital

Tokyo, , Japan

Site Status

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

Site Status

Wakayama Medical University Hospital

Wakayama, , Japan

Site Status

Institut Kanser Negara - National Cancer Institute

Putrajaya, Kuala Lumpur, Malaysia

Site Status

Hospital Tengku Ampuan Afzan

Kuantan, Pahang, Malaysia

Site Status

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Site Status

Pantai Hospital Kuala Lumpur

Kuala Lumpur, , Malaysia

Site Status

Sarawak General Hospital

Kuching, , Malaysia

Site Status

Centrum Onkologii im. Prof. Franciszka Lukaszczyka

Bydgoszcz, , Poland

Site Status

Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie

Gliwice, , Poland

Site Status

Swietokrzyskie Centrum Onkologii SPZOZ

Kielce, , Poland

Site Status

Przychodnia Lekarska Komed

Konin, , Poland

Site Status

Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc

Olsztyn, , Poland

Site Status

Wojewodzki Szpital im. Zofii z Zamoyskich Tarnowskiej w Tarnobrzegu

Tarnobrzeg, , Poland

Site Status

Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie

Warsaw, , Poland

Site Status

Swietokrzyskie Centrum Onkologii SPZOZ

Kielce, Świętokrzyskie Voivodeship, Poland

Site Status

Belgorod Regional Oncology Dispensary

Belgorod, , Russia

Site Status

Central Clinical Hospital with polyclinic

Moscow, , Russia

Site Status

Moscow Research Oncology Institute named after P.A. Hertsen

Moscow, , Russia

Site Status

SBHI Leningrad Regional Clinical Hospital

Saint Petersburg, , Russia

Site Status

SBHI Samara Regional Clinical Oncology Dispensary

Samara, , Russia

Site Status

Republican Clinical Oncology Dispensary of Republic of Bashkortostan

Ufa, , Russia

Site Status

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Site Status

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, South Korea

Site Status

Gacheon University Gil Medical Center

Incheon, , South Korea

Site Status

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, Spain

Site Status

Hospital General de Alicante

Alicante, , Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital Clinico San Carlos

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status

Hospital Clinico de Valencia

Valencia, , Spain

Site Status

Oncological Institute of Southern Switzerland

Bellinzona, , Switzerland

Site Status

Inselspital Universitatsspital Bern

Bern, , Switzerland

Site Status

Hopitaux Universitaires de Geneve HUG.

Geneva, , Switzerland

Site Status

Kantonsspital Winterthur

Winterthur, , Switzerland

Site Status

Universitaetsspital Zuerich

Zurich, , Switzerland

Site Status

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

Adana, , Turkey (Türkiye)

Site Status

Ankara University Medical Faculty

Ankara, , Turkey (Türkiye)

Site Status

Akdeniz Universitesi Tip Fakultesi

Antalya, , Turkey (Türkiye)

Site Status

Erciyes Universitesi Tip Fakultesi

Kayseri, , Turkey (Türkiye)

Site Status

Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi

Konya, , Turkey (Türkiye)

Site Status

MI Kryviy Rih Center of Dnipropetrovsk Regional Council

Kryvyi Rih, Dnipropetrovsk Oblast, Ukraine

Site Status

Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC

Dnipropetrovsk, , Ukraine

Site Status

Grigoriev Institute for medical Radiology NAMS of Ukraine

Kharkiv, , Ukraine

Site Status

PP PPC Acinus Medical and Diagnostic Centre

Kirovohrad, , Ukraine

Site Status

Kyiv City Clinical Oncological Center

Kyiv, , Ukraine

Site Status

Dobryi Prognoz

Kyiv, , Ukraine

Site Status

Volyn Regional Oncological Dispensary

Lutsk, , Ukraine

Site Status

MI Odessa Regional Oncological Centre

Odesa, , Ukraine

Site Status

Zaporizhzhya Regional Clinical Oncology Center

Zaporizhzhya, , Ukraine

Site Status

Leeds Teaching Hospital NHS Trust. St. James University Hospital

Leeds, , United Kingdom

Site Status

Countries

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United States Australia Canada Denmark Estonia Ireland Israel Italy Japan Malaysia Poland Russia South Korea Spain Switzerland Turkey (Türkiye) Ukraine United Kingdom

References

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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.

Reference Type DERIVED
PMID: 39054476 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2017-001841-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KEYNOTE-654-05/ECHO-305-05

Identifier Type: -

Identifier Source: org_study_id

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