A Study of Pembrolizumab (MK-3475) in Combination With Etoposide/Platinum (Cisplatin or Carboplatin) for Participants With Extensive Stage Small Cell Lung Cancer (MK-3475-604/KEYNOTE-604)

• ClinicalTrials.gov Identifier: NCT03066778
• Recruitment Status: Completed
• First Posted: February 28, 2017
• Results First Posted: December 22, 2020
• Last Update Posted: October 3, 2022
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

Brief Summary:

The purpose of this study is to assess the safety and efficacy of pembrolizumab plus standard of care (SOC) chemotherapy (etoposide/platinum [EP]) in participants with newly diagnosed extensive stage small cell lung cancer (ES-SCLC) who have not previously received systemic therapy for this malignancy.

The primary study hypotheses are that pembrolizumab+EP prolongs Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review (BICR) and Overall Survival (OS) compared with placebo+EP in adult participants with ES-SCLC. In this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

With protocol Amendment 07 (03-Oct-2018), the outcome measure of "Change from Baseline at Weeks 12 and 24 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale" was replaced with a single time point analysis at Week 18.

Condition or disease	Intervention/treatment	Phase
Small Cell Lung Cancer (SCLC)	Biological: Pembrolizumab; Drug: Normal saline solution; Drug: Carboplatin; Drug: Cisplatin; Drug: Etoposide	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 453 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Double-Blind, Placebo-controlled Trial of Pembrolizumab (MK-3475/SCH900475) in Combination With Etoposide/Platinum (Cisplatin or Carboplatin) for the First-line Treatment of Subjects With Extensive Stage Small Cell Lung Cancer (KEYNOTE-604)
• Actual Study Start Date: May 2, 2017
• Actual Primary Completion Date: December 2, 2019
• Actual Study Completion Date: September 21, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pembrolizumab+EP; During each 21-day cycle, participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 PLUS etoposide 100 mg/m^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum therapy (carboplatin titrated to an area under the plasma drug concentration-time curve [AUC] 5 IV on Day 1 OR cisplatin 75 mg/m^2 IV on Day 1). Participants who stop pembrolizumab as a result of obtaining a response of stable disease (SD), partial response (PR), complete response (CR) or those who stop after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, are eligible for up to an additional 1 year of treatment after progressive disease if they meet the criteria for retreatment.	Biological: Pembrolizumab; IV infusion on Day 1 of each cycle prior to chemotherapy; Other Names: MK-3475; KEYTRUDA®; Drug: Carboplatin; IV infusion on Day 1 of each cycle; Other Name: PARAPLATIN®; Drug: Cisplatin; IV infusion on Day 1 of each cycle; Other Name: PLATINOL®; Drug: Etoposide; IV infusion on Days 1, 2 and 3 of each cycle; Other Name: TOPOSAR™
Active Comparator: Placebo+EP; During each 21-day cycle, participants receive placebo (normal saline solution) IV on Day 1 PLUS etoposide 100 mg/m^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum therapy (carboplatin titrated to an AUC 5 IV on Day 1 OR cisplatin 75 mg/m^2 IV on Day 1).	Drug: Normal saline solution; IV infusion on Day 1 of each cycle prior to chemotherapy; Drug: Carboplatin; IV infusion on Day 1 of each cycle; Other Name: PARAPLATIN®; Drug: Cisplatin; IV infusion on Day 1 of each cycle; Other Name: PLATINOL®; Drug: Etoposide; IV infusion on Days 1, 2 and 3 of each cycle; Other Name: TOPOSAR™

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 30.5 months ]
   PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. PD, as determined by RECIST 1.1, was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The PFS was calculated using the non-parametric Kaplan-Meier method for censored data and presented for the first course of study treatment per protocol.
2. Overall Survival (OS) [ Time Frame: Up to approximately 30.5 months ]
   OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow up. The OS was calculated using the non-parametric Kaplan-Meier method for censored data and presented for the first course of study treatment per protocol.

Secondary Outcome Measures :

1. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 30.5 months ]
   ORR was defined as the percentage of participants who achieve a best objective response of complete response (CR) or partial response (PR) per RECIST 1.1. CR was defined as the disappearance of all target lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions taking as a reference the baseline sum diameters. In this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The ORR was calculated using the Miettinen & Nurminen method stratified by type of platinum therapy (carboplatin or cisplatin), baseline ECOG performance status (0 or 1), and baseline LDH (≤ or > upper limit of normal) and presented for the first course of study treatment per protocol.
2. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 30.5 months ]
   DOR was defined as the time from first documented evidence of a Complete Response (CR) or Partial Response (PR) per RECIST 1.1 until progressive disease (PD) per RECIST 1.1 or death due to any cause, whichever occurred first. CR was defined as the disappearance of all target lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions taking as a reference the baseline sum diameters. PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. In this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data and is presented for the first course of study treatment per protocol.
3. Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to approximately 30.5 months ]
   An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have had a causal relationship with this treatment. An adverse event could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an adverse event. The number of participants who experienced an AE was reported for each arm according to the treatment received and is presented for the first course of study treatment per protocol.
4. Number of Participants Discontinuing Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 26 months ]
   An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have had a causal relationship with this treatment. An adverse event could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an adverse event. The number of participants who discontinued due to an AE was reported for each arm according to the treatment received and is presented for the first course of study treatment per protocol.
5. Number of Participants Experiencing Any Grade 3 to 5 Adverse Events (AE) as Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE 4.03) [ Time Frame: Up to approximately 30.5 months ]
   The CTCAE uses Grades 1 through 5 correlating to AE severity criteria. Grade 1=mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2=moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3=severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4=life-threatening consequences; urgent intervention indicated. Grade 5=death related to AE. The number of participants who experienced any Grade 3 to 5 AE was reported for each arm according to the treatment received and is presented for the first course of study treatment per protocol.
6. Change From Baseline at Week 18 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale [ Time Frame: Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 18 ]
   EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores are transformed to a range of 0 to 100 using a standard EORTC algorithm. Change from baseline scores were calculated using a constrained longitudinal data analysis (cLDA) model. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. Data are presented for the first course of study treatment per protocol.
7. Change From Baseline at Week 12 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale [ Time Frame: Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 12 ]
   EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. Per protocol, data were to be presented for the first course of study treatment.
8. Change From Baseline at Week 24 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale [ Time Frame: Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 24 ]
   EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. Per protocol, data were to be presented for the first course of study treatment.
9. Time to True Deterioration (TTD) in the Composite Endpoint of Cough, Chest Pain, and Dyspnea Using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and Lung Cancer Module 13 (QLQ-LC13) [ Time Frame: Day 1 of Cycles 1-9, Day 1 of every other cycle for Cycles 10-17 and 30 days after last dose of study treatment (Up to approximately 27 months) ]
   TTD in patient-reported lung cancer symptoms of cough (QLQ-LC-13 Item 1), chest pain (QLQ-LC-13 Item 10), and dyspnea (QLQ-C30 Item 8) was a composite endpoint defined as the time to first onset of ≥10 point deterioration from baseline in an item confirmed by a second adjacent ≥10 point deterioration. The QLQ-LC13 consists of 13 measures of lung cancer symptoms and side effects from chemotherapy and radiation. It is scored on a 4-point scale (1=none, 2=a little, 3=quite a bit, 4=very much). Scores were transformed to a range of 0 to 100 using a standard algorithm. Higher scores represented increasing symptom severity. TTD was calculated using the product-limit Kaplan-Meier method for censored data and is presented for the first course of study treatment per protocol.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Has a documented new diagnosis of SCLC by histology or cytology from brushing, washing, or needle aspiration of a defined lesion. Participants who do not have histology samples (defined as core or excisional biopsy, or resections) will need to undergo a new biopsy to provide a tissue sample.
• Has extensive-stage disease defined as Stage IV (T any, N any, M 1a/b) by the American Joint Committee on Cancer (AJCC), Seventh Edition
• Has ≥1 lesion that meets the criteria for measurable, as defined by RECIST 1.1, and is appropriate for selection as a target lesion, as determined by local site investigator/radiology assessment
• Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
• Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Has a life expectancy of ≥3 months
• Has adequate organ function
• Female and male participants of childbearing potential must be willing to use an adequate method of contraception, starting with the first dose of study treatment through 120 days after the last dose of study treatment and up to 180 days after last dose of chemotherapeutic agents

Exclusion Criteria:

• Has received prior systemic therapy for the treatment of SCLC
• Is currently participating and receiving study treatment or has participated in a study of an investigational agent and received study treatment or used an investigational device within 4 weeks of the first dose of treatment for another health-related problem
• Is expected to require any other form of antineoplastic therapy for SCLC, including radiation therapy, while on study. (Prophylactic cranial irradiation will be possible for those participants with stable disease or better at the completion of the 4 cycles of chemotherapy with or without pembrolizumab.)
• Has known central nervous system (ie, brain and/or spinal cord) metastases and/or carcinomatous meningitis. Participants with brain metastases may participate only if they satisfy all of the following:
• Has completed treatment (eg, whole brain radiation treatment [WBRT], stereotactic radiosurgery, or equivalent) ≥14 days prior to the first dose of study treatment,
• Has no evidence of new or enlarging brain metastases confirmed by post-treatment repeat brain imaging performed ≥3 weeks after pre-treatment brain imaging, and
• Is neurologically stable without the need for steroids for ≥7 days before first dose of study treatment.
• Has had major surgery within 3 weeks prior to receiving the first dose of study treatment or has not recovered adequately from toxicity and/or complications from an intervention prior to receiving the first dose of study treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has a known history of interstitial lung disease
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
• Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
• Has a known history of, or active, neurologic paraneoplastic syndrome
• Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, and/or abdominal carcinomatosis
• Has a history of a severe hypersensitivity reaction to treatment with another monoclonal antibody
• Is taking chronic systemic steroids (in doses exceeding 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of study treatment
• Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
• Has received a live vaccine within 30 days prior to the first dose of study treatment
• Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis factor receptor superfamily member 9 [TNFRSF9, OX-40, CD137]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial
• Has severe hypersensitivity (Grade ≥3) to pembrolizumab and/or any of its excipients
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of Hepatitis B or known active Hepatitis C virus infection
• Has a known history of active TB (Bacillus Tuberculosis)
• Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study starting with the screening visit through 120 days after the last dose of study treatment through and up to 180 days after last dose of chemotherapeutic agents

Contacts and Locations

Locations

United States, Florida

Baptist Health Medical Group Oncology, LLC ( Site 8000)

Miami, Florida, United States, 33176

United States, Illinois

Rush University Medical Center ( Site 1215)

Chicago, Illinois, United States, 60612

North Shore University Health System ( Site 1216)

Evanston, Illinois, United States, 60201

United States, Indiana

Community Hospital ( Site 1207)

Munster, Indiana, United States, 46321

United States, Maryland

Weinberg Cancer Institute at Franklin Square ( Site 1210)

Baltimore, Maryland, United States, 21237

United States, Massachusetts

Massachusetts General Hospital ( Site 1203)

Boston, Massachusetts, United States, 02114

Beth Israel Deaconess Medical Center ( Site 1206)

Boston, Massachusetts, United States, 02215

Dana-Farber Cancer Institute [Boston] ( Site 1201)

Boston, Massachusetts, United States, 02215

United States, Michigan

University of Michigan ( Site 1217)

Ann Arbor, Michigan, United States, 48109-5936

Henry Ford Health System ( Site 1221)

Detroit, Michigan, United States, 48202

United States, Minnesota

Minnesota Oncology Hematology, PA ( Site 8001)

Minneapolis, Minnesota, United States, 55404

United States, Mississippi

Hattiesburg Clinic ( Site 1205)

Hattiesburg, Mississippi, United States, 39401

United States, Missouri

Mercy Hospital Saint Louis ( Site 1213)

Saint Louis, Missouri, United States, 63141

United States, Nevada

Comprehensive Cancer Centers of Nevada ( Site 8004)

Henderson, Nevada, United States, 89074

United States, New Jersey

Memorial Sloan-Kettering Cancer Center At Basking Ridge ( Site 1226)

Basking Ridge, New Jersey, United States, 07920

Memorial Sloan Kettering Cancer Center- Monmouth ( Site 1225)

Middletown, New Jersey, United States, 07748

United States, New York

Montefiore Einstein Center for Cancer Care - Main site ( Site 1204)

Bronx, New York, United States, 10461

Montefiore Medical Center ( Site 1222)

Bronx, New York, United States, 10467

Memorial Sloan-Kettering Cancer Center at Commack ( Site 1227)

Commack, New York, United States, 11725

Memorial Sloan Kettering Cancer Center ( Site 1229)

Harrison, New York, United States, 10604

Memorial Sloan Kettering Cancer Center ( Site 1211)

New York, New York, United States, 10065

Memorial Sloan Kettering Cancer Center - Rockville Centre ( Site 1228)

Rockville Centre, New York, United States, 11570

United States, North Carolina

Duke University Medical Center ( Site 1214)

Durham, North Carolina, United States, 27710

United States, South Carolina

Bon Secours St. Francis Health Sytem ( Site 1212)

Greenville, South Carolina, United States, 29607

United States, Tennessee

Tennessee Oncology, PLLC/The Sarah Cannon Research Institute ( Site 1230)

Nashville, Tennessee, United States, 37203

United States, Texas

Texas Oncology ( Site 8002)

Austin, Texas, United States, 78745

Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 8003)

Dallas, Texas, United States, 75246

Australia, New South Wales

Blacktown Hospital ( Site 0004)

Blacktown, New South Wales, Australia, 2148

Southern Medical Day Care Centre ( Site 0001)

Wollongong, New South Wales, Australia, 2500

Australia, Western Australia

St John of God ( Site 0006)

Murdoch, Western Australia, Australia, 6150

Australia

Lyell McEwin Hospital ( Site 0002)

Elizabeth Vale, Australia, 5112

St Vincents Hospital Melbourne ( Site 0005)

Fitzroy, Australia, 3065

Canada, Manitoba

Cancer Care Manitoba ( Site 0159)

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Nova Scotia

Nova Scotia Health Authority ( Site 0157)

Halifax, Nova Scotia, Canada, B3H 1V7

Canada, Ontario

William Osler Health System (Brampton Civic Hospital) ( Site 0161)

Brampton, Ontario, Canada, L6R 3J7

Kingston Health Sciences Centre ( Site 0155)

Kingston, Ontario, Canada, K7L 2V7

Sunnybrook Research Institute ( Site 0151)

Toronto, Ontario, Canada, M4N 3M5

Canada, Quebec

CISSS de la Monteregie-Centre ( Site 0152)

Greenfield Park, Quebec, Canada, J4V 2H1

CISSS-CA Hotel Dieu de Levis ( Site 0154)

Lévis, Quebec, Canada, G6V 3Z1

CIUSSS Ouest de l'Ile - St-Mary's Hospital ( Site 0158)

Montreal, Quebec, Canada, H3T 1M5

St. Jerome Medical Research Inc. ( Site 0160)

St-Jerome, Quebec, Canada, J7Z 5T3

Chile

Instituto Nacional del Cancer ( Site 0207)

Santiago, Region Metropolitana, Chile, 8380455

Health and Care Chile ( Site 0202)

Santiago, Chile, 7500006

Fundacion Arturo Lopez Perez FALP ( Site 0203)

Santiago, Chile, 7500921

Pontificia Universidad Catolica de Chile ( Site 0206)

Santiago, Chile, 8330032

Clinica Universidad Catolica del Maule ( Site 0208)

Talca, Chile, 3465584

France

CHRU de Lille - Hopital Albert Calmette ( Site 0353)

Lille, France, 59037

C.H.R.U. De Limoges ( Site 0358)

Limoges, France, 87042

CHU Nantes - Hopital Laennec ( Site 0363)

Nantes, France, 44805

Centre Antoine Lacassagne ( Site 0362)

Nice, France, 06189

Hopital Tenon ( Site 0360)

Paris, France, 75020

Institut de Cancerologie Jean-Godinot ( Site 0351)

Reims, France, 51726

CHU de Toulouse - Hopital Larrey ( Site 0354)

Toulouse, France, 31059

Germany

Evangelische Lungenklinik Berlin ( Site 0403)

Berlin, Germany, 13125

Medizinische Fakultaet Carl Gustav Carus der TU Dresden ( Site 0411)

Dresden, Germany, 01307

Florence Nightingale Krankenhaus ( Site 0413)

Duesseldorf, Germany, 40489

SRH Waldklinikum Gera GmbH ( Site 0405)

Gera, Germany, 07548

Asklepios Klinikum Harburg ( Site 0412)

Hamburg, Germany, 21075

Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0401)

Heidelberg, Germany, 69126

Philipps-Universitat Marburg ( Site 0414)

Marburg, Germany, 35032

Universitaetsklinikum Tuebingen ( Site 0404)

Tuebingen, Germany, 72076

Hungary

Orszagos Onkologiai Intezet ( Site 0453)

Budapest, Pest, Hungary, 1122

Orszagos Koranyi TBC es Pulmonologiai Intezet ( Site 0452)

Budapest, Hungary, 1121

Orszagos Koranyi TBC es Pulmonologiai Intezet ( Site 0458)

Budapest, Hungary, 1121

Orszagos Koranyi TBC es Pulmonologiai Intezet ( Site 0459)

Budapest, Hungary, 1121

Veszprem Megyei Tudogyogyintezet ( Site 0454)

Farkasgyepu, Hungary, 8582

Petz Aladar Megyei Oktato Korhaz ( Site 0460)

Gyor, Hungary, 9023

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz ( Site 0456)

Szekesfehervar, Hungary, 8000

Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0451)

Szolnok, Hungary, 5000

Zala Megyei Szent Rafael Korhaz ( Site 0457)

Zalaegerszeg, Hungary, 8900

Ireland

St Vincents University Hospital ( Site 1456)

Dublin, Ireland, D04 Y8V0

St James Hospital ( Site 1452)

Dublin, Ireland, D08 K0Y5

Israel

Soroka Medical Center ( Site 0505)

Beer Sheva, Israel, 8489501

Ramban Medical Center - Dept. Hemato. & B. Marrow Transplant ( Site 0502)

Haifa, Israel, 3525408

Meir Medical Center ( Site 0503)

Kfar Saba, Israel, 4428164

Rabin Medical Center ( Site 0504)

Petah Tikva, Israel, 5262000

Chaim Sheba Medical Center. ( Site 0501)

Ramat-Gan, Israel, 5265601

Japan

National Hospital Organization Nagoya Medical Center ( Site 0615)

Nagoya, Aichi, Japan, 460-0001

National Cancer Center Hospital East ( Site 0613)

Kashiwa, Chiba, Japan, 277-8577

National Hospital Organization Shikoku Cancer Center ( Site 0614)

Matsuyama, Ehime, Japan, 791-0280

Kurume University Hospital ( Site 0609)

Kurume, Fukuoka, Japan, 830-0011

Hyogo Cancer Center ( Site 0611)

Akashi, Hyogo, Japan, 673-8558

Kanagawa Cancer Center ( Site 0618)

Yokohama, Kanagawa, Japan, 241-8515

Sendai Kousei Hospital ( Site 0602)

Sendai, Miyagi, Japan, 980-0873

National Hospital Organization Kinki-chuo Chest Medical Center ( Site 0608)

Sakai, Osaka, Japan, 591-8555

Shizuoka Cancer Center Hospital and Research Institute ( Site 0607)

Sunto-gun, Shizuoka, Japan, 411-8777

National Hospital Organization Yamaguchi Ube Medical Center ( Site 0601)

Ube, Yamaguchi, Japan, 755-0241

National Hospital Organization Kyushu Medical Center ( Site 0617)

Fukuoka, Japan, 810-8563

Hiroshima University Hospital ( Site 0604)

Hiroshima, Japan, 734-8551

Niigata Cancer Center Hospital ( Site 0610)

Niigata, Japan, 951-8566

Osaka International Cancer Institute ( Site 0616)

Osaka, Japan, 541-8567

The Cancer Institute Hospital of JFCR ( Site 0606)

Tokyo, Japan, 135-8550

Wakayama Medical University Hospital ( Site 0612)

Wakayama, Japan, 641-8509

Korea, Republic of

Inje University Haeundae Paik Hospital ( Site 0905)

Busan, Korea, Republic of, 48108

National Cancer Center ( Site 0904)

Goyang-si, Korea, Republic of, 10408

Severance Hospital Yonsei University Health System ( Site 0903)

Seoul, Korea, Republic of, 03722

Asan Medical Center ( Site 0901)

Seoul, Korea, Republic of, 05505

Samsung Medical Center ( Site 0902)

Seoul, Korea, Republic of, 06351

New Zealand

Canterbury Regional Cancer & Blood Services ( Site 0701)

Christchurch, New Zealand, 8011

Poland

Mazowiecki Szpital Onkologiczny ( Site 0757)

Wieliszew, Mazowieckie, Poland, 05-135

Przychodnia Lekarska Komed ( Site 0769)

Konin, Poland, 62-500

Krakowski Szpital Specjalistyczny im. Jana Pawla II ( Site 0768)

Krakow, Poland, 31-202

Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli ( Site 0767)

Lublin, Poland, 20-090

SKPP UM im. Karola Marcinkowkiego w Poznaniu ( Site 0766)

Poznan, Poland, 60-569

Wielkopolskie Centrum Pulmonologii i Torakochirurgii ( Site 0762)

Poznan, Poland, 60-569

Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu ( Site 0756)

Torun, Poland, 87-100

Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie ( Site 0751)

Warszawa, Poland, 02-781

Dolnoslaskie Centrum Onkologii we Wroclawiu ( Site 0771)

Wroclaw, Poland, 53-413

Russian Federation

Belgorod Regional Oncology Dispensary ( Site 0804)

Belgorod, Russian Federation, 308010

N.N. Blokhin NMRCO ( Site 0801)

Moscow, Russian Federation, 115478

SBI of Stavropol region Pyatigorskiy Oncologic dispensary ( Site 0811)

Pyatigorsk, Russian Federation, 357502

SBHI Leningrad Regional Clinical Hospital ( Site 0803)

Saint Petersburg, Russian Federation, 194291

Municipal Clinical Oncology Center ( Site 0802)

Saint Petersburg, Russian Federation, 198255

Spain

Hospital Universitario Insular de Gran Canaria ( Site 0952)

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

Complejo Hospitalario Universitario de A Coruna ( Site 0953)

A Coruna, Spain, 15006

Hospital del Mar ( Site 0956)

Barcelona, Spain, 08003

Hospital Universitari Vall d Hebron ( Site 0951)

Barcelona, Spain, 08035

Hospital Ciudad de Jaen ( Site 0957)

Jaen, Spain, 23007

Hospital General Universitario Gregorio Maranon ( Site 0958)

Madrid, Spain, 28007

Hospital Universitario Fundacion Jimenez Diaz ( Site 0954)

Madrid, Spain, 28040

Hospital Clinico Universitario de Valencia ( Site 0955)

Valencia, Spain, 46010

Switzerland

Kantonsspital Graubuenden ( Site 1403)

Chur, Switzerland, 7000

CHUV Centre Hospitalier Universitaire Vaudois ( Site 1405)

Lausanne, Switzerland, 1011

Universitaetsspital Zuerich ( Site 1404)

Zuerich, Switzerland, 8091

Taiwan

Kaohsiung Chang Gung Memorial Hospital of the C.G.M.F. ( Site 1005)

Kaohsiung, Taiwan, 83301

China Medical University Hospital. ( Site 1003)

Taichung, Taiwan, 40447

Taichung Veterans General Hospital ( Site 1007)

Taichung, Taiwan, 40705

National Cheng Kung University Hospital ( Site 1004)

Tainan, Taiwan, 704

Chi Mei Medical Center Liuying ( Site 1006)

Tainan, Taiwan, 736

National Taiwan University Hospital ( Site 1001)

Taipei, Taiwan, 10002

Taipei Veterans General Hospital ( Site 1002)

Taipei, Taiwan, 11217

Turkey

Ege Universitesi Tıp Fakultesi ( Site 1052)

Izmir, Bornova, Turkey, 35100

Baskent University Adana Dr. Turgut Noyan EAH ( Site 1057)

Adana, Turkey, 01250

Ankara UTF ( Site 1055)

Ankara, Turkey, 06100

Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1060)

Ankara, Turkey, 06100

Dr. Abdurrahman Yurtaslan Ankara Onkoloji EAH ( Site 1053)

Ankara, Turkey, 06200

Trakya Uni. Tip Fakultesi ( Site 1063)

Edirne, Turkey, 22030

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1058)

Istanbul, Turkey, 34098

Medipol Hastanesi ( Site 1066)

Istanbul, Turkey, 34214

Medeniyet Uni. Goztepe Egitim ve Arast. Hast. ( Site 1064)

Istanbul, Turkey, 34722

Medical Park Izmir Hospital ( Site 1051)

Izmir, Turkey, 35575

Kocaeli Universitesi Tip Fakultesi ( Site 1061)

Kocaeli, Turkey, 41380

Inonu Universitesi Tip Fakultesi ( Site 1059)

Malatya, Turkey, 44280

United Kingdom

Birmingham Heartlands Hospital ( Site 1162)

Birmingham, United Kingdom, B9 5SS

St James s University Hospital ( Site 1161)

Leeds, United Kingdom, LS9 7TF

North Middlesex Hospital ( Site 1151)

London, United Kingdom, N18 1QX

Maidstone Hospital ( Site 1155)

Maidstone, United Kingdom, ME16 9QQ

Mount Vernon Cancer Centre ( Site 1156)

Northwood, United Kingdom, HA6 2RN

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme LLC:

Study Protocol and Statistical Analysis Plan  [PDF] April 23, 2019

More Information

Additional Information:

Merck Oncology Clinical Trials Information 

Publications of Results:

Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csoszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gumus M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. doi: 10.1200/JCO.20.00793. Epub 2020 May 29.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03066778
• Other Study ID Numbers: 3475-604; 173744 ( Registry Identifier: JAPIC-CTI ); MK-3475-604 ( Other Identifier: Merck ); KEYNOTE-604 ( Other Identifier: Merck ); 2016-004309-15 ( EudraCT Number )
• First Posted: February 28, 2017
• Results First Posted: December 22, 2020
• Last Update Posted: October 3, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme LLC:

Extensive stage small cell lung cancer (ES-SCLC); Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death Ligand 1 (PDL1, PD-L1); Programmed Cell Death Ligand 2 (PDL2, PD-L2)

Additional relevant MeSH terms:

Lung Neoplasms; Small Cell Lung Carcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carboplatin; Pembrolizumab; Etoposide; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors