Study of Pemetrexed + Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Adults With Tyrosine Kinase Inhibitor- (TKI)-Resistant Epidermal Growth Factor Receptor- (EGFR)-Mutated Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-789/KEYNOTE-789)

A Randomized, Double-Blind, Phase 3 Study of Pemetrexed + Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in TKI-resistant EGFR-mutated Tumors in Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Participants (KEYNOTE-789)

The purpose of this study is to evaluate the efficacy and safety of pemetrexed plus platinum chemotherapy (carboplatin or cisplatin) with or without pembrolizumab (MK-3475; KEYTRUDA®) in the treatment of adults with the following types of tyrosine kinase inhibitor (TKI)-resistant, epidermal growth factor receptor (EGFR)-mutated, metastatic non-squamous non-small cell lung cancer (NSCLC) tumors: 1) TKI-failures (including osimertinib [TAGRISSO®] failure) with T790M-negative mutation tumors, 2) T790M-positive mutation tumors with prior exposure to osimertinib, and 3) first-line osimertinib failure regardless of T790M mutation status.

The primary study hypotheses are that the combination of pembrolizumab plus chemotherapy has superior efficacy compared to saline placebo plus chemotherapy in terms of: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review, and 2) Overall Survival (OS). This study will be considered to have met its success criteria if the combination of pembrolizumab plus chemotherapy is superior to saline placebo plus chemotherapy in terms of PFS or OS.

Upon study completion, participants are discontinued and may be enrolled in a pembrolizumab extension study, if available.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Biological: pembrolizumab; Drug: carboplatin; Drug: cisplatin; Drug: pemetrexed; Drug: saline solution

• Study Type: Interventional
• Enrollment (Actual): 492
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris OBrien Lifehouse ( Site 0200)
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital ( Site 0201)
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Health ( Site 0202)
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health ( Site 0203)
• Brazil
  • Sao Paulo, Brazil, 01246-000
    • Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 1903)
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil, 59075-740
      • Liga Norte Riograndense Contra o Cancer ( Site 1909)
  • Rio Grande Do Sul
    • Ijui, Rio Grande Do Sul, Brazil, 98700-000
      • Hospital de Caridade de Ijui ( Site 1907)
    • Lajeado, Rio Grande Do Sul, Brazil, 95900-010
      • Hospital Bruno Born ( Site 1913)
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre ( Site 1905)
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1904)
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784-400
      • Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 1911)
    • Ribeirao Preto, Sao Paulo, Brazil, 14048-900
      • Hosp. Clinicas da Fac. de Medicina de Ribeirao Preto - USP ( Site 1912)
• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • William Osler Health System ( Site 0100)
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences, Odette Cancer Centre ( Site 0102)
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre ( Site 0104)
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital ( Site 0105)
• China
  • Anhui
    • Hefei, Anhui, China, 230088
      • The First Affiliated Hospital of Anhui Medical University ( Site 0721)
  • Beijing
    • Beijing, Beijing, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences ( Site 0717)
    • Beijing, Beijing, China, 100032
      • Peking Union Medical College Hospital ( Site 0703)
    • Beijing, Beijing, China, 100036
      • Beijing Cancer Hospital ( Site 0718)
  • Chongqing
    • Chongqing, Chongqing, China, 400038
      • Southwest Hospital, The Third Military Medical University ( Site 0725)
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital ( Site 0723)
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • The Affiliated Tumour Hospital of Harbin Medical University ( Site 0706)
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital ( Site 0711)
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital ( Site 0722)
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Central South University ( Site 0710)
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Jiangsu Cancer Hospital ( Site 0719)
  • Jilin
    • Chang chun, Jilin, China, 130021
      • The First Hospital of Jilin University ( Site 0702)
    • Changchun, Jilin, China, 130103
      • Jilin Cancer Hospital ( Site 0705)
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Chest Hospital ( Site 0700)
    • Shanghai, Shanghai, China, 200433
      • Zhongshan Hospital Fudan University ( Site 0712)
  • Shanxi
    • XI An, Shanxi, China, 710038
      • Tangdu Hospital ( Site 0708)
    • XI An, Shanxi, China, 710061
      • The First Affiliated Hospital of Xi an Jiaotong University ( Site 0709)
  • Xinjiang
    • Urumqi, Xinjiang, China, 830000
      • Affiliated Tumor Hospital of Xinjiang Medical University ( Site 0701)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital.Zhejiang University ( Site 0713)
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital School of Medicine, Zhejiang University ( Site 0715)
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital ( Site 0716)
• France
  • Auvergne
    • Lyon, Auvergne, France, 69008
      • Centre Leon Berard ( Site 0801)
  • Calvados
    • Caen, Calvados, France, 14033
      • CHU Caen Service de Pneumologie ( Site 0804)
  • Cote-d'Or
    • Dijon, Cote-d'Or, France, 21000
      • Centre Georges Francois Leclerc ( Site 0809)
  • Doubs
    • Besancon, Doubs, France, 25030
      • Hopital Jean Minjoz Besancon ( Site 0805)
  • Hauts-de-Seine
    • Antony, Hauts-de-Seine, France, 92160
      • Hopital Prive d'Antony ( Site 0811)
  • Indre-et-Loire
    • Tours, Indre-et-Loire, France, 37044
      • C.H.U. de Tours - Hopital Bretonneau ( Site 0806)
  • Meurthe-et-Moselle
    • Nancy, Meurthe-et-Moselle, France, 54100
      • Centre D Oncologie de Gentilly ( Site 0810)
  • Sarthe
    • Le Mans, Sarthe, France, 72000
      • Clinique Victor Hugo ( Site 0802)
  • Vienne
    • Poitiers, Vienne, France, 86021
      • CHU Poitiers ( Site 0803)
• Germany
  • Hamburg, Germany, 21075
    • Asklepios Klinikum Hamburg ( Site 0908)
  • Baden-Wurttemberg
    • Gerlingen, Baden-Wurttemberg, Germany, 70839
      • Robert Bosch Krankenhaus Klinik Schillerhoehe ( Site 0904)
    • Mannheim, Baden-Wurttemberg, Germany, 68167
      • Universitaetsklinikum Mannheim ( Site 0911)
  • Bayern
    • Wuerzburg, Bayern, Germany, 97074
      • Klinikum Wuerzburg Mitte gGmbH ( Site 0901)
  • Niedersachsen
    • Oldenburg, Niedersachsen, Germany, 26121
      • Pius Hospital Oldenburg ( Site 0905)
  • Nordrhein-Westfalen
    • Duesseldorf, Nordrhein-Westfalen, Germany, 40489
      • Florence Nightingale Krankenhaus ( Site 0912)
    • Essen, Nordrhein-Westfalen, Germany, 45136
      • Kliniken Essen-Mitte ( Site 0900)
    • Muenster, Nordrhein-Westfalen, Germany, 48149
      • Universitaetsklinikum Muenster ( Site 0906)
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Medizinische Fakultaet Carl Gustav Carus der TU Dresden ( Site 0907)
• Hong Kong
  • Hong Kong, Hong Kong
    • Hong Kong Integrated Oncology Centre ( Site 0304)
  • Hong Kong, Hong Kong
    • Queen Mary Hospital ( Site 0301)
  • Hong Kong, Hong Kong
    • Queen Mary Hospital ( Site 0303)
  • Kowloon, Hong Kong
    • Hong Kong United Oncology Centre ( Site 0306)
  • Tuen Mun, Hong Kong
    • Tuen Mun Hospital ( Site 0305)
• Israel
  • HaDarom
    • Ashkelon, HaDarom, Israel, 7830604
      • Barzilai Medical Center ( Site 1706)
    • Beer-Sheva, HaDarom, Israel, 8457108
      • Soroka Medical Center ( Site 1702)
  • HaMerkaz
    • Kfar-Saba, HaMerkaz, Israel, 4428164
      • Meir Medical Center ( Site 1701)
    • Petah Tikva, HaMerkaz, Israel, 4941492
      • Rabin Medical Center ( Site 1704)
  • HaTsafon
    • Afula, HaTsafon, Israel, 1834111
      • Ha Emek Medical Center ( Site 1707)
  • Heifa
    • Haifa, Heifa, Israel, 3109601
      • Rambam Medical Center ( Site 1703)
  • Tell Abib
    • Ramat Gan, Tell Abib, Israel, 5265601
      • Chaim Sheba Medical Center. ( Site 1700)
    • Tel Aviv, Tell Abib, Israel, 6423906
      • Sourasky Medical Center ( Site 1705)
• Italy
  • Bari, Italy, 70124
    • IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1305)
  • Firenze, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi ( Site 1301)
  • Napoli, Italy, 80131
    • Azienda Ospedaliera dei Colli V. Monaldi ( Site 1306)
  • Roma, Italy, 00128
    • Universita Campus Bio-Medico di Roma ( Site 1304)
  • Lombardia
    • Milano, Lombardia, Italy, 20141
      • Istituto Europeo di Oncologia ( Site 1303)
  • Messina
    • Taormina, Messina, Italy, 98039
      • Ospedale San Vincenzo di Taormina ( Site 1302)
  • Torino
    • Orbassano, Torino, Italy, 10043
      • AOU San Luigi Gonzaga di Orbassano ( Site 1300)
• Japan
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center ( Site 0621)
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital ( Site 0605)
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital ( Site 0610)
  • Okayama, Japan, 700-8558
    • Okayama University Hospital ( Site 0614)
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute ( Site 0611)
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital ( Site 0603)
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital ( Site 0615)
  • Tokyo, Japan, 113-8677
    • Tokyo Metropolitan Komagome Hospital ( Site 0618)
  • Wakayama, Japan, 641-8510
    • Wakayama Medical University Hospital ( Site 0613)
  • Aichi
    • Nagoya, Aichi, Japan, 460-0001
      • National Hospital Organization Nagoya Medical Center ( Site 0608)
    • Nagoya, Aichi, Japan, 464-8681
      • Aichi Cancer Center Hospital ( Site 0612)
    • Toyoake, Aichi, Japan, 470-1192
      • Fujita Health University Hospital ( Site 0619)
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East ( Site 0601)
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center ( Site 0616)
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
      • Hyogo Cancer Center ( Site 0604)
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8641
      • Kanazawa University Hospital ( Site 0617)
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center ( Site 0609)
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital ( Site 0606)
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center Hospital and Research Institute ( Site 0602)
• Korea, Republic of
  • Chungcheongbuk-do [Chungbuk]
    • Cheongju si, Chungcheongbuk-do [Chungbuk], Korea, Republic of, 28644
      • Chungbuk National University Hospital ( Site 0404)
  • Incheon-gwangyeoksi [Incheon]
    • Incheon, Incheon-gwangyeoksi [Incheon], Korea, Republic of, 21565
      • Gachon University Gil Medical Center ( Site 0408)
  • Kyonggi-do
    • Gyeonggi-do, Kyonggi-do, Korea, Republic of, 10408
      • National Cancer Center ( Site 0400)
    • Seongnam-si, Kyonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital ( Site 0405)
  • Seoul-teukbyeolsi [Seoul]
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 03080
      • Seoul National University Hospital ( Site 0402)
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 05505
      • Asan Medical Center ( Site 0407)
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 06351
      • Samsung Medical Center ( Site 0403)
    • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 06591
      • The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 0406)
  • Ulsan-Kwangyokshi
    • Ulsan, Ulsan-Kwangyokshi, Korea, Republic of, 44033
      • Ulsan University Hospital ( Site 0401)
• Mexico
  • Mexico City, Mexico, 14050
    • Medica Sur S.A.B de C.V. ( Site 2003)
  • Oaxaca, Mexico, 68000
    • Oaxaca Site Management Organization SC ( Site 2001)
  • Tlalpan, Mexico, 14080
    • Instituto Nacional de Cancerologia. ( Site 2007)
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Instituto Jaliscience de Cancerologia ( Site 2000)
• Spain
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal ( Site 1101)
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre ( Site 1103)
  • Malaga, Spain, 29010
    • Complejo Hospitalario Carlos Haya de Malaga ( Site 1107)
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena ( Site 1104)
  • Barcelona [Barcelona]
    • Badalona, Barcelona [Barcelona], Spain, 08916
      • Hospitalo Univ. Germans Trias i Pujol ( Site 1100)
    • Barcelona, Barcelona [Barcelona], Spain, 08025
      • Hospital de la Santa Creu i Sant Pau ( Site 1102)
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Hospital Universitari Vall d Hebron ( Site 1106)
• Sweden
  • Ostergotlands Lan [se-05]
    • Linkoping, Ostergotlands Lan [se-05], Sweden, 581 85
      • Linkopings Universitetssjukhus ( Site 1504)
  • Skane Lan [se-12]
    • Lund, Skane Lan [se-12], Sweden, 221 85
      • Skanes Universitetssjukhus Lund ( Site 1503)
  • Stockholms Lan [se-01]
    • Solna, Stockholms Lan [se-01], Sweden, 171 64
      • Karolinska Universitetssjukhuset Solna ( Site 1500)
  • Vastra Gotalands Lan [se-14]
    • Goteborg, Vastra Gotalands Lan [se-14], Sweden, 413 45
      • Sahlgrenska Universitetssjukhuset ( Site 1502)
• Taiwan
  • Changhua, Taiwan, 50006
    • Changhua Christian Hospital ( Site 0509)
  • Hsinchu, Taiwan, 300
    • National Taiwan University Hospital Hsin-Chu Branch ( Site 0511)
  • Hualien, Taiwan, 970
    • Hualien Tzu Chi Medical Center-Hospital ( Site 0510)
  • Kaohsiung, Taiwan, 833
    • Kaohsiung Chang Gung Memorial Hospital ( Site 0507)
  • New Taipei, Taiwan, 235
    • Taipei Medical University Shuang Ho Hospital ( Site 0508)
  • Taichung, Taiwan, 40447
    • China Medical University Hospital ( Site 0505)
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital ( Site 0504)
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital ( Site 0506)
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital ( Site 0500)
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital ( Site 0501)
  • Taipei, Taiwan, 104
    • Mackay Memorial Hospital ( Site 0503)
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation. Linkou ( Site 0502)
  • New Taipei
    • New Taipei City, New Taipei, Taiwan, 231
      • Taipei Tzu Chi Hospital ( Site 0512)
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital ( Site 1002)
  • Leeds, United Kingdom, LS9 7TF
    • St James s University Hospital ( Site 1008)
  • Romford, United Kingdom, RM7 0AG
    • Barking Havering and Redbridge University Hospitals NHS Trust Queen s Hospital ( Site 1004)
  • Brighton And Hove
    • Brighton, Brighton And Hove, United Kingdom, BN2 5BE
      • Sussex University Hospitals ( Site 1003)
  • Edinburgh, City Of
    • Edinburgh, Edinburgh, City Of, United Kingdom, EH4 2XU
      • Western General Hospital ( Site 1009)
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary ( Site 1000)
  • London, City Of
    • London, London, City Of, United Kingdom, NW1 2PG
      • University College London Hospitals NHS Foundation Trust ( Site 1006)
    • London, London, City Of, United Kingdom, SW10 9NH
      • Chelsea & Westminster Hospital ( Site 1001)
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center ( Site 0070)
    • Monterey, California, United States, 93940
      • Pacific Cancer Care ( Site 0058)
    • Orange, California, United States, 92868
      • UC Irvine Medical Center/Chao Family Comprehensive Cancer Center ( Site 0092)
    • Santa Rosa, California, United States, 95403
      • St. Joseph Heritage Healthcare ( Site 0003)
  • Illinois
    • Evanston, Illinois, United States, 60201
      • North Shore University Health System ( Site 0030)
  • Iowa
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regioinal Cancer Center dba June E. Nylen Cancer Center ( Site 0065)
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Southdale Cancer Care, University of Minnesota Medical Center- Edina ( Site 0048)
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Lukes Hospital of Kansas City ( Site 0060)
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology P.C ( Site 8000)
    • Lake Success, New York, United States, 11042
      • Monter Cancer Center ( Site 0054)
    • New York, New York, United States, 10022
      • Memorial Sloan Kettering Cancer Center-Rockerfeller Patient Pavilion ( Site 0049)
    • White Plains, New York, United States, 10601
      • White Plains Hospital Center for Cancer Care ( Site 0014)
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center ( Site 0097)
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest ( Site 0037)
  • Texas
    • Dallas, Texas, United States, 75235
      • Parkland Health & Hospital System ( Site 2102)
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center at Dallas ( Site 0035)
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists ( Site 0001)
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Emily Couric Clinical Cancer Center ( Site 0020)
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital & the Medical College of Wisconsin ( Site 0041)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of Stage IV non-squamous NSCLC.
• Documentation of tumor activating EGFR mutation, specifically either DEL19 or L858R.
• Investigator-determined radiographic disease progression per RECIST 1.1 after treatment with an EGFR TKI therapy: a) Participants previously treated with 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib) are required to have confirmed documented absence of EGFR T790M mutation; b) Participants with confirmed acquired T790M mutation after 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib) are required to have osimertinib TKI treatment failure prior to enrollment; c) Participants previously failed osimertinib TKI treatment as 1st line therapy are eligible regardless of their EGFR T790M mutation status. Note: TKI washout period for all participants is 1 week or 2 half-lives after last treatment dose, whichever is longer. TKI washout should be completed prior to first dose of study treatment.
• Measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
• Provided archival tumor tissue sample or newly obtained (no anti-neoplastic therapy since biopsy) core or excisional biopsy of a tumor lesion not previously irradiated.
• Life expectancy of at least 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study treatment but before randomization.
• Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after last dose of chemotherapeutic agents.
• Female participants must not be pregnant, not breastfeeding, and must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents.
• Adequate organ function.

Exclusion Criteria:

• Predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the participant is ineligible.
• Symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
• 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-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein-4 [CTLA-4], OX-40, CD137).
• Received prior systemic cytotoxic chemotherapy or investigational agent(s), excluding EGFR TKIs, for metastatic NSCLC. [Notes: 1) Prior treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic NSCLC. 2) If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. 3) Prior exposure to traditional medicine(s) is allowed as long as therapy was discontinued at least 4 weeks prior to the first dose of study treatment.]
• Received prior radiotherapy within 2 weeks of start of study treatment or has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Received a live vaccine within 30 days prior to the first dose of study treatment.
• Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.
• Known additional malignancy that is progressing or has required active treatment within the past 5 years. (Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.)
• Known active untreated CNS metastases and/or carcinomatous meningitis.
• Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
• Known sensitivity to any component of cisplatin, carboplatin, or pemetrexed.
• Active autoimmune disease that has required systemic treatment in past 2 years.
• History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Active infection requiring systemic therapy.
• Known history of human immunodeficiency virus (HIV) infection.
• Known history of Hepatitis B or known active Hepatitis C virus.
• Known history of active tuberculosis (TB; Bacillus tuberculosis)
• Pregnant, 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 pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembro+Pemetrexed+Chemo; Participants receive pembrolizumab (pembro) 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo) (either carboplatin Area Under the Curve [AUC] 5 via IV infusion Q3W for 4 cycles [Cycles 1-4] or cisplatin 75 mg/m^2 via IV infusion Q3W for 4 cycles [Cycles 1-4]).	Biological: pembrolizumab; IV infusion; Other Names: MK-3475; Drug: carboplatin; IV infusion; Drug: cisplatin; IV infusion; Drug: pemetrexed; IV infusion
Active Comparator: Placebo+Pemetrexed+Chemo; Participants receive normal saline solution via IV infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo)(either carboplatin AUC 5 via IV infusion Q3W for 4 cycles [Cycles 1-4] or cisplatin 75 mg/m^2 via IV infusion Q3W for 4 cycles [Cycles 1-4]).	Drug: carboplatin; IV infusion; Drug: cisplatin; IV infusion; Drug: pemetrexed; IV infusion; Drug: saline solution; IV infusion; Other Names: Normal saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PFS was assessed by blinded independent central review (BICR) using RECIST 1.1. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions is also considered PD. The PFS presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.	Up to ~40 months
Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. The OS presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.	Up to ~51 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per RECIST 1.1	ORR was assessed by BICR using RECIST 1.1. ORR is defined as the percentage of participants in the analysis population who experience a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The ORR for participants is presented.	Up to ~51 months
Duration of Response (DOR) Per RECIST 1.1	DOR was assessed by BICR using RECIST 1.1. For participants who experience a response of CR or PR, DOR is defined as the time from the earliest date of qualifying response until earliest date of PD or death from any cause, whichever comes first. The DOR presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.	Up to ~51 months
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 Item (QLQ-C30) Global Health Status (Item 29) Scale Score	The EORTC QLQ-C30 is a 30-item Patient Reported Outcome (PRO) questionnaire developed to assess the quality of life of cancer patients. For Global Health Status, participants are asked "How would you rate your overall health during the past week?" Individual responses are given on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better outcome. The change from baseline in EORTC-QLQ-C30 score for Global Health Status is presented.	Baseline and Week 18
Time to True Deterioration (TTD) in the EORTC Questionnaire Composite Endpoint of Cough, Chest Pain or Dyspnea	TTD is the time from baseline to first onset of 10 points or more deterioration from baseline with confirmation by the subsequent visit of 10 points or more deterioration from baseline in the composite endpoint of cough [EORTC QLQ-Lung Cancer Module 13 (LC13) Item 1; How much did you cough?], chest pain [EORTC QLQ-LC13 Item 10; Have you had pain in your chest?], or dyspnea [EORTC QLQ-C30 Item 8; Were you short of breath?]. Individual responses are given on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating a better outcome. The TTD was analyzed using the product-limit (Kaplan-Meier) method for censored data. The time to true deterioration in the composite endpoint of cough, chest pain or dyspnea is presented.	Baseline and up to ~51 months
Percentage of Participants Who Experienced an Adverse Event (AE)	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who experienced an AE is presented.	Up to ~44 months
Percentage of Participants Who Discontinued Study Treatment Due to AEs	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who discontinued study treatment due to an adverse event is presented.	Up to ~41 months
Change From Baseline in EORTC-QLQ-C30 Quality of Life (Item 30) Scale Score	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. For Quality of Life, participants are asked "How would you rate your overall quality of life during the past week?" Individual responses are given on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better outcome. The change from baseline in EORTC-QLQ-C30 score for Quality of Life is presented.	Baseline and Week 18

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2018
• Primary Completion (Actual): January 17, 2023
• Study Completion (Actual): October 2, 2023

Study Registration Dates

• First Submitted: April 23, 2018
• First Submitted That Met QC Criteria: April 23, 2018
• First Posted (Actual): May 4, 2018

Study Record Updates

• Last Update Posted (Estimated): January 17, 2024
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: PD-1; PD-L1; PD1; PDL1
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Carboplatin; Pembrolizumab; Pharmaceutical Solutions; Pemetrexed
• Other Study ID Numbers: 3475-789; MK-3475-789 (Other Identifier: Merck Protocol Number); 184019 (Registry Identifier: JAPIC); 2017-004188-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No