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)
Small Cell Lung Cancer (SCLC)
About this trial
This is an interventional treatment trial for Small Cell Lung Cancer (SCLC) focused on measuring 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)
Eligibility 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
Sites / Locations
- Baptist Health Medical Group Oncology, LLC ( Site 8000)
- Rush University Medical Center ( Site 1215)
- North Shore University Health System ( Site 1216)
- Community Hospital ( Site 1207)
- Weinberg Cancer Institute at Franklin Square ( Site 1210)
- Massachusetts General Hospital ( Site 1203)
- Beth Israel Deaconess Medical Center ( Site 1206)
- Dana-Farber Cancer Institute [Boston] ( Site 1201)
- University of Michigan ( Site 1217)
- Henry Ford Health System ( Site 1221)
- Minnesota Oncology Hematology, PA ( Site 8001)
- Hattiesburg Clinic ( Site 1205)
- Mercy Hospital Saint Louis ( Site 1213)
- Comprehensive Cancer Centers of Nevada ( Site 8004)
- Memorial Sloan-Kettering Cancer Center At Basking Ridge ( Site 1226)
- Memorial Sloan Kettering Cancer Center- Monmouth ( Site 1225)
- Montefiore Einstein Center for Cancer Care - Main site ( Site 1204)
- Montefiore Medical Center ( Site 1222)
- Memorial Sloan-Kettering Cancer Center at Commack ( Site 1227)
- Memorial Sloan Kettering Cancer Center ( Site 1229)
- Memorial Sloan Kettering Cancer Center ( Site 1211)
- Memorial Sloan Kettering Cancer Center - Rockville Centre ( Site 1228)
- Duke University Medical Center ( Site 1214)
- Bon Secours St. Francis Health Sytem ( Site 1212)
- Tennessee Oncology, PLLC/The Sarah Cannon Research Institute ( Site 1230)
- Texas Oncology ( Site 8002)
- Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 8003)
- Blacktown Hospital ( Site 0004)
- Southern Medical Day Care Centre ( Site 0001)
- St John of God ( Site 0006)
- Lyell McEwin Hospital ( Site 0002)
- St Vincents Hospital Melbourne ( Site 0005)
- Cancer Care Manitoba ( Site 0159)
- Nova Scotia Health Authority ( Site 0157)
- William Osler Health System (Brampton Civic Hospital) ( Site 0161)
- Kingston Health Sciences Centre ( Site 0155)
- Sunnybrook Research Institute ( Site 0151)
- CISSS de la Monteregie-Centre ( Site 0152)
- CISSS-CA Hotel Dieu de Levis ( Site 0154)
- CIUSSS Ouest de l'Ile - St-Mary's Hospital ( Site 0158)
- St. Jerome Medical Research Inc. ( Site 0160)
- Instituto Nacional del Cancer ( Site 0207)
- Health and Care Chile ( Site 0202)
- Fundacion Arturo Lopez Perez FALP ( Site 0203)
- Pontificia Universidad Catolica de Chile ( Site 0206)
- Clinica Universidad Catolica del Maule ( Site 0208)
- CHRU de Lille - Hopital Albert Calmette ( Site 0353)
- C.H.R.U. De Limoges ( Site 0358)
- CHU Nantes - Hopital Laennec ( Site 0363)
- Centre Antoine Lacassagne ( Site 0362)
- Hopital Tenon ( Site 0360)
- Institut de Cancerologie Jean-Godinot ( Site 0351)
- CHU de Toulouse - Hopital Larrey ( Site 0354)
- Evangelische Lungenklinik Berlin ( Site 0403)
- Medizinische Fakultaet Carl Gustav Carus der TU Dresden ( Site 0411)
- Florence Nightingale Krankenhaus ( Site 0413)
- SRH Waldklinikum Gera GmbH ( Site 0405)
- Asklepios Klinikum Harburg ( Site 0412)
- Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0401)
- Philipps-Universitat Marburg ( Site 0414)
- Universitaetsklinikum Tuebingen ( Site 0404)
- Orszagos Onkologiai Intezet ( Site 0453)
- Orszagos Koranyi TBC es Pulmonologiai Intezet ( Site 0452)
- Orszagos Koranyi TBC es Pulmonologiai Intezet ( Site 0458)
- Orszagos Koranyi TBC es Pulmonologiai Intezet ( Site 0459)
- Veszprem Megyei Tudogyogyintezet ( Site 0454)
- Petz Aladar Megyei Oktato Korhaz ( Site 0460)
- Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz ( Site 0456)
- Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0451)
- Zala Megyei Szent Rafael Korhaz ( Site 0457)
- St Vincents University Hospital ( Site 1456)
- St James Hospital ( Site 1452)
- Soroka Medical Center ( Site 0505)
- Ramban Medical Center - Dept. Hemato. & B. Marrow Transplant ( Site 0502)
- Meir Medical Center ( Site 0503)
- Rabin Medical Center ( Site 0504)
- Chaim Sheba Medical Center. ( Site 0501)
- National Hospital Organization Nagoya Medical Center ( Site 0615)
- National Cancer Center Hospital East ( Site 0613)
- National Hospital Organization Shikoku Cancer Center ( Site 0614)
- Kurume University Hospital ( Site 0609)
- Hyogo Cancer Center ( Site 0611)
- Kanagawa Cancer Center ( Site 0618)
- Sendai Kousei Hospital ( Site 0602)
- National Hospital Organization Kinki-chuo Chest Medical Center ( Site 0608)
- Shizuoka Cancer Center Hospital and Research Institute ( Site 0607)
- National Hospital Organization Yamaguchi Ube Medical Center ( Site 0601)
- National Hospital Organization Kyushu Medical Center ( Site 0617)
- Hiroshima University Hospital ( Site 0604)
- Niigata Cancer Center Hospital ( Site 0610)
- Osaka International Cancer Institute ( Site 0616)
- The Cancer Institute Hospital of JFCR ( Site 0606)
- Wakayama Medical University Hospital ( Site 0612)
- Inje University Haeundae Paik Hospital ( Site 0905)
- National Cancer Center ( Site 0904)
- Severance Hospital Yonsei University Health System ( Site 0903)
- Asan Medical Center ( Site 0901)
- Samsung Medical Center ( Site 0902)
- Canterbury Regional Cancer & Blood Services ( Site 0701)
- Mazowiecki Szpital Onkologiczny ( Site 0757)
- Przychodnia Lekarska Komed ( Site 0769)
- Krakowski Szpital Specjalistyczny im. Jana Pawla II ( Site 0768)
- Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli ( Site 0767)
- SKPP UM im. Karola Marcinkowkiego w Poznaniu ( Site 0766)
- Wielkopolskie Centrum Pulmonologii i Torakochirurgii ( Site 0762)
- Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu ( Site 0756)
- Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie ( Site 0751)
- Dolnoslaskie Centrum Onkologii we Wroclawiu ( Site 0771)
- Belgorod Regional Oncology Dispensary ( Site 0804)
- N.N. Blokhin NMRCO ( Site 0801)
- SBI of Stavropol region Pyatigorskiy Oncologic dispensary ( Site 0811)
- SBHI Leningrad Regional Clinical Hospital ( Site 0803)
- Municipal Clinical Oncology Center ( Site 0802)
- Hospital Universitario Insular de Gran Canaria ( Site 0952)
- Complejo Hospitalario Universitario de A Coruna ( Site 0953)
- Hospital del Mar ( Site 0956)
- Hospital Universitari Vall d Hebron ( Site 0951)
- Hospital Ciudad de Jaen ( Site 0957)
- Hospital General Universitario Gregorio Maranon ( Site 0958)
- Hospital Universitario Fundacion Jimenez Diaz ( Site 0954)
- Hospital Clinico Universitario de Valencia ( Site 0955)
- Kantonsspital Graubuenden ( Site 1403)
- CHUV Centre Hospitalier Universitaire Vaudois ( Site 1405)
- Universitaetsspital Zuerich ( Site 1404)
- Kaohsiung Chang Gung Memorial Hospital of the C.G.M.F. ( Site 1005)
- China Medical University Hospital. ( Site 1003)
- Taichung Veterans General Hospital ( Site 1007)
- National Cheng Kung University Hospital ( Site 1004)
- Chi Mei Medical Center Liuying ( Site 1006)
- National Taiwan University Hospital ( Site 1001)
- Taipei Veterans General Hospital ( Site 1002)
- Ege Universitesi Tıp Fakultesi ( Site 1052)
- Baskent University Adana Dr. Turgut Noyan EAH ( Site 1057)
- Ankara UTF ( Site 1055)
- Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1060)
- Dr. Abdurrahman Yurtaslan Ankara Onkoloji EAH ( Site 1053)
- Trakya Uni. Tip Fakultesi ( Site 1063)
- Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1058)
- Medipol Hastanesi ( Site 1066)
- Medeniyet Uni. Goztepe Egitim ve Arast. Hast. ( Site 1064)
- Medical Park Izmir Hospital ( Site 1051)
- Kocaeli Universitesi Tip Fakultesi ( Site 1061)
- Inonu Universitesi Tip Fakultesi ( Site 1059)
- Birmingham Heartlands Hospital ( Site 1162)
- St James s University Hospital ( Site 1161)
- North Middlesex Hospital ( Site 1151)
- Maidstone Hospital ( Site 1155)
- Mount Vernon Cancer Centre ( Site 1156)
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Pembrolizumab+EP
Placebo+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.
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).