AzTrials
AzTrials

Non-small Cell Lung CancerPhase 3NCT03515837

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 Phase 3 study testing pembrolizumab, pemetrexed and carboplatin in people with Non-small Cell Lung Cancer, run by Merck Sharp & Dohme LLC at 158 sites in 17 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
pembrolizumab, pemetrexed and carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
492 participants
Where
158 sitesin 17 countries
Study dates
29 Jun 2018to 2 Oct 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

158 sites in 17 countries.

158 sites in 17 countries

China21 sites

  • Cancer Hospital Chinese Academy of Medical Sciences ( Site 0717)

    Beijing, Beijing Municipality, 100021

  • Peking Union Medical College Hospital ( Site 0703)

    Beijing, Beijing Municipality, 100032

  • Beijing Cancer Hospital ( Site 0718)

    Beijing, Beijing Municipality, 100036

  • The First Hospital of Jilin University ( Site 0702)

    Changchun, Jilin, 130021

  • Jilin Cancer Hospital ( Site 0705)

    Changchun, Jilin, 130103

  • Xiangya Hospital of Central South University ( Site 0710)

    Changsha, Hunan, 410008

  • Hunan Cancer Hospital ( Site 0722)

    Changsha, Hunan, 410013

  • Southwest Hospital, The Third Military Medical University ( Site 0725)

    Chongqing, Chongqing Municipality, 400038

  • Fujian Cancer Hospital ( Site 0723)

    Fuzhou, Fujian, 350014

  • The First Affiliated Hospital.Zhejiang University ( Site 0713)

    Hangzhou, Zhejiang, 310003

  • Sir Run Run Shaw Hospital School of Medicine, Zhejiang University ( Site 0715)

    Hangzhou, Zhejiang, 310016

  • Zhejiang Cancer Hospital ( Site 0716)

    Hangzhou, Zhejiang, 310022

  • The Affiliated Tumour Hospital of Harbin Medical University ( Site 0706)

    Harbin, Heilongjiang, 150081

  • The First Affiliated Hospital of Anhui Medical University ( Site 0721)

    Hefei, Anhui, 230088

  • Jiangsu Cancer Hospital ( Site 0719)

    Nanjing, Jiangsu, 210000

  • Shanghai Chest Hospital ( Site 0700)

    Shanghai, Shanghai Municipality, 200030

  • Zhongshan Hospital Fudan University ( Site 0712)

    Shanghai, Shanghai Municipality, 200433

  • Affiliated Tumor Hospital of Xinjiang Medical University ( Site 0701)

    Ürümqi, Xinjiang, 830000

  • Tangdu Hospital ( Site 0708)

    Xi’an, Shanxi, 710038

  • The First Affiliated Hospital of Xi an Jiaotong University ( Site 0709)

    Xi’an, Shanxi, 710061

  • Henan Cancer Hospital ( Site 0711)

    Zhengzhou, Henan, 450008

Other trials in China

United States19 sites

  • New York Oncology Hematology P.C ( Site 8000)

    Albany, New York, 12208

  • Emily Couric Clinical Cancer Center ( Site 0020)

    Charlottesville, Virginia, 22903

  • Parkland Health & Hospital System ( Site 2102)

    Dallas, Texas, 75235

  • University of Texas Southwestern Medical Center at Dallas ( Site 0035)

    Dallas, Texas, 75390

  • Southdale Cancer Care, University of Minnesota Medical Center- Edina ( Site 0048)

    Edina, Minnesota, 55435

  • North Shore University Health System ( Site 0030)

    Evanston, Illinois, 60201

  • Saint Lukes Hospital of Kansas City ( Site 0060)

    Kansas City, Missouri, 64111

  • Monter Cancer Center ( Site 0054)

    Lake Success, New York, 11042

  • Cedars-Sinai Medical Center ( Site 0070)

    Los Angeles, California, 90048

  • Froedtert Hospital & the Medical College of Wisconsin ( Site 0041)

    Milwaukee, Wisconsin, 53226

  • Pacific Cancer Care ( Site 0058)

    Monterey, California, 93940

  • Memorial Sloan Kettering Cancer Center-Rockerfeller Patient Pavilion ( Site 0049)

    New York, New York, 10022

  • UC Irvine Medical Center/Chao Family Comprehensive Cancer Center ( Site 0092)

    Orange, California, 92868

  • Providence Portland Medical Center ( Site 0097)

    Portland, Oregon, 97213

  • Kaiser Permanente Northwest ( Site 0037)

    Portland, Oregon, 97227

  • Utah Cancer Specialists ( Site 0001)

    Salt Lake City, Utah, 84106

  • St. Joseph Heritage Healthcare ( Site 0003)

    Santa Rosa, California, 95403

  • Siouxland Regioinal Cancer Center dba June E. Nylen Cancer Center ( Site 0065)

    Sioux City, Iowa, 51101

  • White Plains Hospital Center for Cancer Care ( Site 0014)

    White Plains, New York, 10601

Other trials in United States

Japan19 sites

  • Hyogo Cancer Center ( Site 0604)

    Akashi, Hyōgo, 673-8558

  • National Hospital Organization Kyushu Medical Center ( Site 0621)

    Fukuoka, 810-8563

  • Kyushu University Hospital ( Site 0605)

    Fukuoka, 812-8582

  • Kansai Medical University Hospital ( Site 0606)

    Hirakata, Osaka, 573-1191

  • Kanazawa University Hospital ( Site 0617)

    Kanazawa, Ishikawa-ken, 920-8641

  • National Cancer Center Hospital East ( Site 0601)

    Kashiwa, Chiba, 277-8577

  • National Hospital Organization Shikoku Cancer Center ( Site 0616)

    Matsuyama, Ehime, 791-0280

  • National Hospital Organization Nagoya Medical Center ( Site 0608)

    Nagoya, Aichi-ken, 460-0001

  • Aichi Cancer Center Hospital ( Site 0612)

    Nagoya, Aichi-ken, 464-8681

  • Niigata Cancer Center Hospital ( Site 0610)

    Niigata, 951-8566

  • Okayama University Hospital ( Site 0614)

    Okayama, 700-8558

  • Osaka International Cancer Institute ( Site 0611)

    Osaka, 541-8567

  • Shizuoka Cancer Center Hospital and Research Institute ( Site 0602)

    Sunto-gun, Shizuoka, 411-8777

  • National Cancer Center Hospital ( Site 0603)

    Tokyo, 104-0045

  • Toranomon Hospital ( Site 0615)

    Tokyo, 105-8470

  • Tokyo Metropolitan Komagome Hospital ( Site 0618)

    Tokyo, 113-8677

  • Fujita Health University Hospital ( Site 0619)

    Toyoake, Aichi-ken, 470-1192

  • Wakayama Medical University Hospital ( Site 0613)

    Wakayama, 641-8510

  • Kanagawa Cancer Center ( Site 0609)

    Yokohama, Kanagawa, 241-8515

Other trials in Japan

Taiwan13 sites

  • Changhua Christian Hospital ( Site 0509)

    Changhua, 50006

  • National Taiwan University Hospital Hsin-Chu Branch ( Site 0511)

    Hsinchu, 300

  • Hualien Tzu Chi Medical Center-Hospital ( Site 0510)

    Hualien City, Hualien, 970

  • Kaohsiung Chang Gung Memorial Hospital ( Site 0507)

    Kaohsiung City, 833

  • Taipei Tzu Chi Hospital ( Site 0512)

    New Taipei City, New Taipei, 231

  • Taipei Medical University Shuang Ho Hospital ( Site 0508)

    New Taipei City, 235

  • China Medical University Hospital ( Site 0505)

    Taichung, 40447

  • Taichung Veterans General Hospital ( Site 0504)

    Taichung, 40705

  • National Cheng Kung University Hospital ( Site 0506)

    Tainan, 704

  • National Taiwan University Hospital ( Site 0500)

    Taipei, 100

  • Mackay Memorial Hospital ( Site 0503)

    Taipei, 104

  • Taipei Veterans General Hospital ( Site 0501)

    Taipei, 11217

  • Chang Gung Medical Foundation. Linkou ( Site 0502)

    Taoyuan, 333

Other trials in Taiwan

France9 sites

  • Hopital Prive d'Antony ( Site 0811)

    Antony, Hauts-de-Seine, 92160

  • Hopital Jean Minjoz Besancon ( Site 0805)

    Besançon, Doubs, 25030

  • CHU Caen Service de Pneumologie ( Site 0804)

    Caen, Calvados, 14033

  • Centre Georges Francois Leclerc ( Site 0809)

    Dijon, Cote-d'Or, 21000

  • Clinique Victor Hugo ( Site 0802)

    Le Mans, Sarthe, 72000

  • Centre Leon Berard ( Site 0801)

    Lyon, Auvergne, 69008

  • Centre D Oncologie de Gentilly ( Site 0810)

    Nancy, Meurthe-et-Moselle, 54100

  • CHU Poitiers ( Site 0803)

    Poitiers, Vienne, 86021

  • C.H.U. de Tours - Hopital Bretonneau ( Site 0806)

    Tours, Indre-et-Loire, 37044

Other trials in France

Germany9 sites

  • Medizinische Fakultaet Carl Gustav Carus der TU Dresden ( Site 0907)

    Dresden, Saxony, 01307

  • Florence Nightingale Krankenhaus ( Site 0912)

    Düsseldorf, North Rhine-Westphalia, 40489

  • Kliniken Essen-Mitte ( Site 0900)

    Essen, North Rhine-Westphalia, 45136

  • Robert Bosch Krankenhaus Klinik Schillerhoehe ( Site 0904)

    Gerlingen, Baden-Wurttemberg, 70839

  • Asklepios Klinikum Hamburg ( Site 0908)

    Hamburg, 21075

  • Universitaetsklinikum Mannheim ( Site 0911)

    Mannheim, Baden-Wurttemberg, 68167

  • Universitaetsklinikum Muenster ( Site 0906)

    Münster, North Rhine-Westphalia, 48149

  • Pius Hospital Oldenburg ( Site 0905)

    Oldenburg, Lower Saxony, 26121

  • Klinikum Wuerzburg Mitte gGmbH ( Site 0901)

    Würzburg, Bavaria, 97074

Other trials in Germany

South Korea9 sites

  • Chungbuk National University Hospital ( Site 0404)

    Cheongju-si, Chungcheongbuk-do [Chungbuk], 28644

  • National Cancer Center ( Site 0400)

    Gyeonggi-do, Kyonggi-do, 10408

  • Gachon University Gil Medical Center ( Site 0408)

    Incheon, Incheon-gwangyeoksi [Incheon], 21565

  • Seoul National University Bundang Hospital ( Site 0405)

    Seongnam-si, Kyonggi-do, 13620

  • Seoul National University Hospital ( Site 0402)

    Seoul, Seoul-teukbyeolsi [Seoul], 03080

  • Asan Medical Center ( Site 0407)

    Seoul, Seoul-teukbyeolsi [Seoul], 05505

  • Samsung Medical Center ( Site 0403)

    Seoul, Seoul-teukbyeolsi [Seoul], 06351

  • The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 0406)

    Seoul, Seoul-teukbyeolsi [Seoul], 06591

  • Ulsan University Hospital ( Site 0401)

    Ulsan, Ulsan-Kwangyokshi, 44033

Other trials in South Korea

Brazil8 sites

  • Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 1911)

    Barretos, São Paulo, 14784-400

  • Hospital de Caridade de Ijui ( Site 1907)

    Ijuí, Rio Grande do Sul, 98700-000

  • Hospital Bruno Born ( Site 1913)

    Lajeado, Rio Grande do Sul, 95900-010

  • Liga Norte Riograndense Contra o Cancer ( Site 1909)

    Natal, Rio Grande do Norte, 59075-740

  • Hospital de Clinicas de Porto Alegre ( Site 1905)

    Porto Alegre, Rio Grande do Sul, 90035-903

  • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1904)

    Porto Alegre, Rio Grande do Sul, 90610-000

  • Hosp. Clinicas da Fac. de Medicina de Ribeirao Preto - USP ( Site 1912)

    Ribeirão Preto, São Paulo, 14048-900

  • Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 1903)

    São Paulo, 01246-000

Other trials in Brazil

Israel8 sites

  • Ha Emek Medical Center ( Site 1707)

    Afula, Northern District, 1834111

  • Barzilai Medical Center ( Site 1706)

    Ashkelon, Southern District, 7830604

  • Soroka Medical Center ( Site 1702)

    Beersheba, Southern District, 8457108

  • Rambam Medical Center ( Site 1703)

    Haifa, Heifa, 3109601

  • Meir Medical Center ( Site 1701)

    Kfar Saba, Central District, 4428164

  • Rabin Medical Center ( Site 1704)

    Petah Tikva, Central District, 4941492

  • Chaim Sheba Medical Center. ( Site 1700)

    Ramat Gan, Tell Abib, 5265601

  • Sourasky Medical Center ( Site 1705)

    Tel Aviv, Tell Abib, 6423906

Other trials in Israel

United Kingdom8 sites

  • Birmingham Heartlands Hospital ( Site 1002)

    Birmingham, B9 5SS

  • Sussex University Hospitals ( Site 1003)

    Brighton, Brighton And Hove, BN2 5BE

  • Western General Hospital ( Site 1009)

    Edinburgh, Edinburgh, City of, EH4 2XU

  • St James s University Hospital ( Site 1008)

    Leeds, LS9 7TF

  • Leicester Royal Infirmary ( Site 1000)

    Leicester, Leicestershire, LE1 5WW

  • University College London Hospitals NHS Foundation Trust ( Site 1006)

    London, London, City of, NW1 2PG

  • Chelsea & Westminster Hospital ( Site 1001)

    London, London, City of, SW10 9NH

  • Barking Havering and Redbridge University Hospitals NHS Trust Queen s Hospital ( Site 1004)

    Romford, RM7 0AG

Other trials in United Kingdom

Italy7 sites

  • IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1305)

    Bari, 70124

  • Azienda Ospedaliero Universitaria Careggi ( Site 1301)

    Florence, 50134

  • Istituto Europeo di Oncologia ( Site 1303)

    Milan, Lombardy, 20141

  • Azienda Ospedaliera dei Colli V. Monaldi ( Site 1306)

    Naples, 80131

  • AOU San Luigi Gonzaga di Orbassano ( Site 1300)

    Orbassano, Torino, 10043

  • Universita Campus Bio-Medico di Roma ( Site 1304)

    Roma, 00128

  • Ospedale San Vincenzo di Taormina ( Site 1302)

    Taormina, Messina, 98039

Other trials in Italy

Spain7 sites

  • Hospitalo Univ. Germans Trias i Pujol ( Site 1100)

    Badalona, Barcelona [Barcelona], 08916

  • Hospital de la Santa Creu i Sant Pau ( Site 1102)

    Barcelona, Barcelona [Barcelona], 08025

  • Hospital Universitari Vall d Hebron ( Site 1106)

    Barcelona, Barcelona [Barcelona], 08035

  • Hospital Ramon y Cajal ( Site 1101)

    Madrid, 28034

  • Hospital Universitario 12 de Octubre ( Site 1103)

    Madrid, 28041

  • Complejo Hospitalario Carlos Haya de Malaga ( Site 1107)

    Málaga, 29010

  • Hospital Universitario Virgen Macarena ( Site 1104)

    Seville, 41009

Other trials in Spain

Hong Kong5 sites

  • Hong Kong Integrated Oncology Centre ( Site 0304)

    Hong Kong

  • Queen Mary Hospital ( Site 0301)

    Hong Kong

  • Queen Mary Hospital ( Site 0303)

    Hong Kong

  • Hong Kong United Oncology Centre ( Site 0306)

    Kowloon

  • Tuen Mun Hospital ( Site 0305)

    Tuenmen

Other trials in Hong Kong

Australia4 sites

  • Eastern Health ( Site 0202)

    Box Hill, Victoria, 3128

  • Chris OBrien Lifehouse ( Site 0200)

    Camperdown, New South Wales, 2050

  • Austin Health ( Site 0203)

    Heidelberg, Victoria, 3084

  • Westmead Hospital ( Site 0201)

    Westmead, New South Wales, 2145

Other trials in Australia

Canada4 sites

  • William Osler Health System ( Site 0100)

    Brampton, Ontario, L6R 3J7

  • Jewish General Hospital ( Site 0105)

    Montreal, Quebec, H3T 1E2

  • Sunnybrook Health Sciences, Odette Cancer Centre ( Site 0102)

    Toronto, Ontario, M4N 3M5

  • Princess Margaret Cancer Centre ( Site 0104)

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Mexico4 sites

  • Instituto Jaliscience de Cancerologia ( Site 2000)

    Guadalajara, Jalisco, 44280

  • Medica Sur S.A.B de C.V. ( Site 2003)

    Mexico City, 14050

  • Oaxaca Site Management Organization SC ( Site 2001)

    Oaxaca City, 68000

  • Instituto Nacional de Cancerologia. ( Site 2007)

    Tlalpan, 14080

Other trials in Mexico

Sweden4 sites

  • Sahlgrenska Universitetssjukhuset ( Site 1502)

    Gothenburg, Vastra Gotalands Lan [se-14], 413 45

  • Linkopings Universitetssjukhus ( Site 1504)

    Linköping, Ostergotlands Lan [se-05], 581 85

  • Skanes Universitetssjukhus Lund ( Site 1503)

    Lund, Skane Lan [se-12], 221 85

  • Karolinska Universitetssjukhuset Solna ( Site 1500)

    Solna, Stockholms Lan [se-01], 171 64

Other trials in Sweden

About this study

Official title: 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.

Being tested
pembrolizumab, pemetrexed, carboplatin, cisplatin, saline solution
Keywords
PD1, PD-1, PDL1, PD-L1
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03515837
Study groupRoleWhat they receive
Pembro+Pemetrexed+ChemoExperimentalParticipants 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]).
Receives: Biological: pembrolizumab; Drug: pemetrexed; Drug: carboplatin; Drug: cisplatin
Placebo+Pemetrexed+ChemoActive comparatorParticipants 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]).
Receives: Drug: pemetrexed; Drug: carboplatin; Drug: cisplatin; Drug: saline solution

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to ~40 months

  2. 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.

    Measured: Up to ~51 months

Secondary outcomes (6)

  1. 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.

    Measured: Up to ~51 months

  2. 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.

    Measured: Up to ~51 months

  3. Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score

    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are each scored on a 7-point scale (1=Very poor to 7=Excellent). The two raw scores were averaged into a combined score, then normalized using linear transformation so each participant's score ranged from 0 to 100 (0=Worst overall health/quality of life and 100=Best overall health/quality of life). The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score is presented.

    Measured: Baseline and Week 18

  4. 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.

    Measured: Baseline and up to ~51 months

  5. 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.

    Measured: Up to ~44 months

  6. 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.

    Measured: Up to ~41 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2018
  2. Study start29 Jun 2018
  3. Primary completion17 Jan 2023
  4. Study completion2 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
492 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03515837
Sponsor's protocol ID
3475-789
Other IDs
MK-3475-789, 184019, 2017-004188-11, 2017
Status last verified
Nov 2024
First submitted
23 Apr 2018
Last updated
22 Nov 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Yang JC, Lee DH, Lee JS, Fan Y, de Marinis F, Iwama E, Inoue T, Rodriguez-Cid J, Zhang L, Yang CT, de la Mora Jimenez E, Zhou J, Perol M, Lee KH, Vicente D, Ichihara E, Riely GJ, Luo Y, Chirovsky D, Pietanza MC, Bhagwati N, Lu S. Phase III KEYNOTE-789 Study of Pemetrexed and Platinum With or Without Pembrolizumab for Tyrosine Kinase Inhibitor-Resistant, EGFR-Mutant, Metastatic Nonsquamous Non-Small Cell Lung Cancer. J Clin Oncol. 2024 Dec;42(34):4029-4039. doi: 10.1200/JCO.23.02747. Epub 2024 Aug 22.

    PubMed 39173098

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing pembrolizumab, pemetrexed and carboplatin in people with Non-small Cell Lung Cancer, run by Merck Sharp & Dohme LLC at 158 sites in 17 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 158 sites in China, United States, Japan, Taiwan, France and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (time frame: Up to ~40 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03515837, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2024.

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