A Study of Pembrolizumab Plus Epacadostat With Platinum-based Chemotherapy Versus Pembrolizumab Plus Platinum-based Chemotherapy Plus Placebo in Metastatic Non-Small Cell Lung Cancer (KEYNOTE-715-06/ECHO-306-06)

NCT03322566 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: KEYNOTE-715-06/ECHO-306-062017-001810-27
• Study Type: interventional
• Target: 233
• Locations: 14 countries
• Sites: 94

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of pembrolizumab plus epacadostat with platinum-based chemotherapy versus pembrolizumab plus platinum-based chemotherapy plus placebo as first-line therapy in participants with metastatic non-small cell lung cancer (NSCLC).

Conditions

Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo

  ORR is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) based on blinded independent central review (BICR).

  Assessed every 12 weeks up to 24 months

Secondary Outcomes (5)

• Progression-free Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo

  Up to 24 months

• Overall Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo

  Up to 24 months

• Duration of Response of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo

  Up to 24 months

• Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Experiencing Adverse Events (AEs)

  Up to 25 months

• Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Discontinuing Study Drug Due to AEs

  Up to 25 months

Study Arms (3)

Pembrolizumab + Chemotherapy + Epacadostat

EXPERIMENTAL

Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m\^2 IV infusion, Q3W + cisplatin 75 mg/m\^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m\^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).

Drug: Pembrolizumab; Drug: Epacadostat; Drug: Platinum-based chemotherapy

Pembrolizumab + Chemotherapy + Placebo

EXPERIMENTAL

Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m\^2 IV infusion, Q3W + cisplatin 75 mg/m\^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m\^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).

Drug: Pembrolizumab; Drug: Platinum-based chemotherapy; Drug: Placebo

Pembrolizumab + Epacadostat

EXPERIMENTAL

Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, BID in each 21 day cycle for up to 35 cycles.

Drug: Pembrolizumab; Drug: Epacadostat

Interventions

Pembrolizumab DRUG

Pembrolizumab administered intravenously every 3 weeks.

Also known as: MK-3475

Pembrolizumab + Chemotherapy + Epacadostat; Pembrolizumab + Chemotherapy + Placebo; Pembrolizumab + Epacadostat

Epacadostat DRUG

Epacadostat administered orally twice daily.

Also known as: INCB024360

Pembrolizumab + Chemotherapy + Epacadostat; Pembrolizumab + Epacadostat

Platinum-based chemotherapy DRUG

Investigator selected one of the following regimens: pemetrexed + cisplatin, pemetrexed + carboplatin, or paclitaxel + carboplatin, depending on histology.

Pembrolizumab + Chemotherapy + Epacadostat; Pembrolizumab + Chemotherapy + Placebo

Placebo DRUG

Matching placebo administered orally twice daily.

Pembrolizumab + Chemotherapy + 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
• 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.
• Provide tumor tissue sample.

You may not qualify if:

• Known untreated central nervous system metastases and/or carcinomatous meningitis
• History of (non-infectious) 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 (94)

Southern Cancer Center, PC

Daphne, Alabama, 36526, United States

Location

Western Regional Medical Center, Inc.

Goodyear, Arizona, 85338, United States

Location

Arizona Oncology Associates PC- HOPE

Tucson, Arizona, 85704, United States

Location

Lynn Cancer Institute

Boca Raton, Florida, 33486, United States

Location

Florida Cancer Specialists (South Region)

Fort Myers, Florida, 33901-8101, United States

Location

Florida Cancer Specialists (North Region)

St. Petersburg, Florida, 33705, United States

Location

PPG-Oncology

Fort Wayne, Indiana, 46845, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MMCORC

Saint Louis Park, Minnesota, 55416, United States

Location

St. Vincent Healthcare Frontier Cancer Center

Billings, Montana, 59102, United States

Location

New York Oncology Hematology P.C

Albany, New York, 12208, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45242, United States

Location

Southwestern Regional Medical Center, Inc.

Tulsa, Oklahoma, 74133, United States

Location

St. Luke's Hospital - Anderson Campus

Easton, Pennsylvania, 18045, 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-Denton South

Denton, Texas, 76210, United States

Location

Oncology & Hematology Assoc. SW Virginia, Inc., DBA Blue Ridge Cancer Care

Blacksburg, Virginia, 24060, United States

Location

Emily Couric Clinical Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Blacktown Hospital

Blacktown, New South Wales, 2148, Australia

Location

Chris OBrien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

The Crown Princess Mary Cancer Centre Westmead

Westmead, New South Wales, 2145, Australia

Location

Southern Medical Day Care Centre

Wollongong, New South Wales, 2500, Australia

Location

MNCCI Port Macquarie Base Hospital

Port Macquarie, New South Wales (Australia), 2444, Australia

Location

Cairns Base Hospital

Cairns, Queensland, 4870, Australia

Location

BCCA-Cancer Centre of the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

Lions Gate Hospital

North Vancouver, British Columbia, V7L 2L7, Canada

Location

CISSS de la Monteregie-Centre

Greenfield Park, Quebec, J4V 2H1, Canada

Location

CSSS de Laval- Hopital de la Cite de la Sante

Laval, Quebec, H7M 3L9, Canada

Location

CIUSSS Ouest de l'Ile - St-Mary's Hospital

Montreal, Quebec, H3T 1M5, Canada

Location

CIUSSS du Nord-de-l'ILe-de-Montreal Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, H4J 1C5, Canada

Location

CHU de Quebec - Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

CIUSSS de la Mauricie-et-du-Centre-du-Quebec

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Zala Megyei Korhaz Pozvai Telephely

Pózva, Zalaegerszeg, 8900, Hungary

Location

Orszagos Koranyi TBC es Pulmonologiai Intezet

Budapest, 1121, Hungary

Location

Veszprem Megyei Tudogyogyintezet

Farkasgyepű, 8582, Hungary

Location

Bekes Megyei Pandy Kalman Korhaz

Gyula, 5700, Hungary

Location

CRU Hungary Kft.

Miskolc, 3529, Hungary

Location

Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet

Szolnok, 5004, Hungary

Location

St Vincents University Hospital

Dublin, Dublin 4, Ireland

Location

Ha Emek Medical Center

Afula, 1834111, Israel

Location

Soroka Medical Center

Beersheba, 8457108, Israel

Location

Rambam Medical Center

Haifa, 3525408, Israel

Location

Meir Medical Center

Kfar Saba, 4428164, Israel

Location

Rabin Medical Center

Petah Tikva, 5262000, Israel

Location

Chaim Sheba Medcal Center

Ramat Gan, 52621, Israel

Location

Centro Di Riferimento Oncologico

Aviano, 33081, Italy

Location

A.O.U. Policlinico Vittorio Emanuele - Presidio Gaspare Rodolico

Catania, 95123, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Ospedale San Gerardo - ASST Monza

Monza, 20900, Italy

Location

Medical Care Research S.A. de C.V.

Mérida, Yucatán, 97070, Mexico

Location

Oaxaca Site Management Organization S.C.

Oaxaca City, 68000, Mexico

Location

FAICIC Clinical Research

Veracruz, 91900, Mexico

Location

Belgorod Regional Oncology Dispensary

Belgorod, 308010, Russia

Location

Udmurtia Republic Regional Clinical Oncology Dispensary

Izhevsk, 426067, Russia

Location

Republican Clinical Oncology Dispensary of Tatarstan MoH

Kazan', 420029, Russia

Location

Central Clinical Hospital with polyclinic

Moscow, 121359, Russia

Location

Moscow Research Oncology Institute

Moscow, 125284, Russia

Location

SBI of Stavropol region Pyatigorskiy Oncologic dispensary

Pyatigorsk, 357502, Russia

Location

SBHI Leningrad Regional Clinical Hospital

Saint Petersburg, 194291, Russia

Location

SBHI Samara Regional Clinical Oncology Dispensary

Samara, 443031, Russia

Location

Oncological Dispensary #2 of Ministry of Health of Krasnodar region

Sochi, 354057, Russia

Location

Tomsk Scientific Research Institute of Oncology

Tomsk, 634028, Russia

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria, Gran Canaria, 35016, Spain

Location

Hospital Juan Ramón Jimenez

Huelva, 21005, Spain

Location

Institut Catala Oncologia de Bellvitge - ICO

L'Hospitalet de Llobregat, 08980, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario La Fe

Valencia, 46026, Spain

Location

Hospital Clinico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Chang Gung Medical Foundation, Kaohsiung Branch

Kaohsiung City, 833, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70457, Taiwan

Location

National Taiwan University Hospital

Taipei, 10048, Taiwan

Location

Chang Gung Medical Foundation, Linkou Branch

Taoyuan District, 33305, Taiwan

Location

Ege Universitesi Tip Fakultesi Hastanesi

Izmir, Bornova, 35100, Turkey (Türkiye)

Location

Baskent Universitesi Adana Uygulama ve Arastirma Hastanesi

Adana, 01120, Turkey (Türkiye)

Location

Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi

Adana, 01330, Turkey (Türkiye)

Location

Hacettepe Universitesi Tip Fakultesi Hastanesi

Ankara, 06100, Turkey (Türkiye)

Location

Uludag Universitesi Tip Fakultesi

Bursa, 16059, Turkey (Türkiye)

Location

Pamukkale Unv. Tip Fak

Denizli, 20070, Turkey (Türkiye)

Location

Istanbul Universitesi Cerrahpasa Tip Fakultesi

Istanbul, 34098, Turkey (Türkiye)

Location

Samsun Medical Park Hastanesi

Samsun, 55200, Turkey (Türkiye)

Location

Namık Kemal University Medical Faculty

Tekirdağ, 59030, Turkey (Türkiye)

Location

Mount Vernon Cancer Centre

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

Western General Hospital

Edinburgh, EH42XU, United Kingdom

Location

North Middlesex Hospital

London, N18 1QX, United Kingdom

Location

Freeman Hospital Newcastle upon Tyne Foundation NHS Trust

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (1)

• Boyer M, Hui R, Urban D, Clingan P, Su WC, Devaux C, Gadgeel S, Garassino M, Leopold L, Daniel J, Munteanu MC, Samkari A, Luo Y, Abreu DR. Pembrolizumab with platinum-based chemotherapy with or without epacadostat as first-line treatment for metastatic non-small cell lung cancer: a randomized, partially double-blind, placebo-controlled phase II study. BMC Cancer. 2024 Jul 25;23(Suppl 1):1250. doi: 10.1186/s12885-022-10427-4.

  PMID: 39054462 DERIVED

MeSH Terms

Conditions

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

Interventions

pembrolizumab; epacadostat; Platinum Compounds

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Inorganic Chemicals

Limitations and Caveats

Data from the final analysis of KEYNOTE-715/ECHO-306 (data cutoff: 13-DEC-2018) indicated that the study did not meet the pre-specified endpoint of improvement in objective response rate (ORR).

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

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
• 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: January 9, 2018
• Primary Completion: December 13, 2018
• Study Completion: October 16, 2020
• Last Updated: January 24, 2022
• Results First Posted: January 29, 2020

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

HU (6); KR (4); TW (5); ME (3); US (21); TU (9); ES (6); GB (4); IE (1); RU (10); AU (6); IT (5); CA (8); IL (6)