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

NCT03322540 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: KEYNOTE-654-05/ECHO-305-052017-001841-28
• Study Type: interventional
• Target: 154
• Locations: 17 countries
• Sites: 100

Brief 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).

Conditions

Lung Cancer

Keywords

non-small cell lung cancer; programmed cell death 1 (PD-1) inhibitor; indoleamine 2; 3-dioxygenase 1 (IDO1) inhibitor

Outcome Measures

Primary Outcomes (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).

  Up to approximately 6 months

Secondary Outcomes (5)

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

  Up to approximately 36 months

• Overall Survival (OS) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo

  Up to approximately 36 months

• Duration of Response (DOR) of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo

  Up to approximately 36 months

• Number of Participants With Adverse Events (AEs)

  Up to 37 months

• Number of Participants Who Discontinued Study Drug Due to AEs

  Up to 37 months

Study Arms (2)

Pembrolizumab + Epacadostat

EXPERIMENTAL

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; Drug: Epacadostat

Pembrolizumab + Placebo

ACTIVE COMPARATOR

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; Drug: Placebo

Interventions

Pembrolizumab DRUG

Pembrolizumab administered intravenously every 3 weeks.

Also known as: MK-3475

Pembrolizumab + Epacadostat; Pembrolizumab + Placebo

Epacadostat DRUG

Epacadostat administered orally twice daily.

Also known as: INCB024360

Pembrolizumab + Epacadostat

Placebo DRUG

Matching placebo administered orally twice daily.

Pembrolizumab + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (101)

Pacific Cancer Medical Center, Inc.

Anaheim, California, 92801, United States

Location

Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

Florida Cancer Specialists (South Region)

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists (North Region)

St. Petersburg, Florida, 33705, United States

Location

Southeastern Regional Medical Center, Inc.

Newnan, Georgia, 30265, United States

Location

Anne Arundel Health System Research Institute

Annapolis, Maryland, 21401, United States

Location

Weinberg Cancer Institute at Franklin Square

Baltimore, Maryland, 21237, United States

Location

Maryland Oncology Hematology, P.A.

Rockville, Maryland, 20850, United States

Location

UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Minnesota Oncology Hematology, PA

Coon Rapids, Minnesota, 55433, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Tennessee Oncology, PLLC/The Sarah Cannon Research Institute

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology, PLLC/The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology-South Austin

Austin, Texas, 78745, United States

Location

Austin Health-Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

St John of God Murdoch Medical Clinic

Murdoch, Western Australia, 6150, Australia

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Moncton Hospital - Horizon Health Network

Moncton, New Brunswick, E1C 6Z8, Canada

Location

William Osler Health System

Brampton, Ontario, L6R 3J7, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

Sault Area Hospital

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Regionshospitalet Herning

Herning, 7400, Denmark

Location

Odense Universitetshospital

Odense, 5000, Denmark

Location

SA Tartu Ulikooli Kliinikum

Tartu, 51014, Estonia

Location

Galway University Hospital

Galway, Connacht, H91 YR71, Ireland

Location

St Vincents University Hospital

Dublin, Dublin 4, Ireland

Location

Soroka Medical Center

Beersheba, 8457108, Israel

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Meir Medical Center

Kfar Saba, 4428164, Israel

Location

Rabin Medical Center

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52621, Israel

Location

IRCCS A.O.U. San Martino - IST

Genova, 16132, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

National Hospital Organization Nagoya Medical Center

Nagoya, Aichi-ken, 460-0001, Japan

Location

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, 791-0280, Japan

Location

Kurume University Hospital

Kurume, Fukuoka, 830-0011, Japan

Location

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Kanagawa Cancer Center

Yokohama, Kanagawa, 241-8515, Japan

Location

Sendai Kousei Hospital

Sendai, Miyagi, 980-0873, Japan

Location

Kansai Medical University Hospital

Hirakata, Osaka, 573-1191, Japan

Location

Kindai University Hospital

Sayama, Osaka, 589-8511, Japan

Location

Shizuoka Cancer Center

Nagaizumi-chō, Shizuoka, 411-8777, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1395, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Niigata Cancer Center Hospital

Niigata, 951-8566, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

Nippon Medical School Hospital

Tokyo, 113-8603, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

Location

Wakayama Medical University Hospital

Wakayama, 641-8509, Japan

Location

Institut Kanser Negara - National Cancer Institute

Putrajaya, Kuala Lumpur, 62250, Malaysia

Location

Hospital Tengku Ampuan Afzan

Kuantan, Pahang, 25100, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Pantai Hospital Kuala Lumpur

Kuala Lumpur, Malaysia

Location

Sarawak General Hospital

Kuching, Malaysia

Location

Centrum Onkologii im. Prof. Franciszka Lukaszczyka

Bydgoszcz, 85-796, Poland

Location

Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie

Gliwice, 44-101, Poland

Location

Swietokrzyskie Centrum Onkologii SPZOZ

Kielce, 25-734, Poland

Location

Przychodnia Lekarska Komed

Konin, 62-500, Poland

Location

Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc

Olsztyn, 10-357, Poland

Location

Wojewodzki Szpital im. Zofii z Zamoyskich Tarnowskiej w Tarnobrzegu

Tarnobrzeg, 39-400, Poland

Location

Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie

Warsaw, 02-781, Poland

Location

Swietokrzyskie Centrum Onkologii SPZOZ

Kielce, Świętokrzyskie Voivodeship, 25-734, Poland

Location

Belgorod Regional Oncology Dispensary

Belgorod, 308010, Russia

Location

Central Clinical Hospital with polyclinic

Moscow, 121359, Russia

Location

Moscow Research Oncology Institute named after P.A. Hertsen

Moscow, 125284, Russia

Location

SBHI Leningrad Regional Clinical Hospital

Saint Petersburg, 194291, Russia

Location

SBHI Samara Regional Clinical Oncology Dispensary

Samara, 443031, Russia

Location

Republican Clinical Oncology Dispensary of Republic of Bashkortostan

Ufa, 450054, Russia

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, 28644, South Korea

Location

Gacheon University Gil Medical Center

Incheon, 21565, South Korea

Location

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, 36312, Spain

Location

Hospital General de Alicante

Alicante, 03010, Spain

Location

Hospital del Mar

Barcelona, 8003, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Clinico de Valencia

Valencia, 46010, Spain

Location

Oncological Institute of Southern Switzerland

Bellinzona, 6500, Switzerland

Location

Inselspital Universitatsspital Bern

Bern, 3010, Switzerland

Location

Hopitaux Universitaires de Geneve HUG.

Geneva, 1211, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

Universitaetsspital Zuerich

Zurich, 8091, Switzerland

Location

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

Adana, 01120, Turkey (Türkiye)

Location

Ankara University Medical Faculty

Ankara, 06100, Turkey (Türkiye)

Location

Akdeniz Universitesi Tip Fakultesi

Antalya, 07059, Turkey (Türkiye)

Location

Erciyes Universitesi Tip Fakultesi

Kayseri, 38039, Turkey (Türkiye)

Location

Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi

Konya, 42080, Turkey (Türkiye)

Location

MI Kryviy Rih Center of Dnipropetrovsk Regional Council

Kryvyi Rih, Dnipropetrovsk Oblast, 50048, Ukraine

Location

Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC

Dnipropetrovsk, 49102, Ukraine

Location

Grigoriev Institute for medical Radiology NAMS of Ukraine

Kharkiv, 61024, Ukraine

Location

PP PPC Acinus Medical and Diagnostic Centre

Kirovohrad, 25001, Ukraine

Location

Kyiv City Clinical Oncological Center

Kyiv, 03115, Ukraine

Location

Dobryi Prognoz

Kyiv, 03126, Ukraine

Location

Volyn Regional Oncological Dispensary

Lutsk, 43018, Ukraine

Location

MI Odessa Regional Oncological Centre

Odesa, 65055, Ukraine

Location

Zaporizhzhya Regional Clinical Oncology Center

Zaporizhzhya, 69040, Ukraine

Location

Leeds Teaching Hospital NHS Trust. St. James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39054476 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; epacadostat

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Lance Leopold, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: With the implementation of Amendment 05 the study is no longer blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2017
• First Posted: October 26, 2017
• Study Start: December 15, 2017
• Primary Completion: January 10, 2019
• Study Completion: November 9, 2020
• Last Updated: August 22, 2025
• Results First Posted: February 5, 2020

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (7); DK (3); PL (8); TU (5); IT (2); JP (17); AU (2); IE (2); RU (6); KR (3); MY (5); IL (5); CH (5); US (15); GB (1); UA (9); CA (5)