AzTrials
AzTrials

Nonsquamous Non-small Cell Lung CancerPhase 3NCT03829319

Safety and Efficacy Study of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-7902-006/E7080-G000-315/LEAP-006)

A Phase 3 study testing Pembrolizumab, Carboplatin and Cisplatin in people with Nonsquamous 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 assess the safety and efficacy of pemetrexed + platinum chemotherapy + pembrolizumab (MK-3475) with or without lenvatinib (MK-7902/E7080) as first-line intervention in adults with metastatic nonsquamous non-small cell lung cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Nonsquamous Non-small Cell Lung Cancer
What is being tested?
Pembrolizumab, Carboplatin and Cisplatin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
761 participants
Where
158 sitesin 17 countries
Study dates
25 Mar 2019to 30 Aug 2024
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 (American Joint Committee on Cancer [AJCC], version 8 or current version), nonsquamous NSCLC.
  • Confirmation that Epidermal Growth Factor Receptor (EGFR), ALK Receptor Tyrosine Kinase (ALK), or ROS1 Receptor Tyrosine Kinase (ROS1)-directed therapy is not indicated as primary treatment (documentation of absence of tumor-activating EGFR mutations AND absence of ALK and ROS1 gene rearrangements OR presence of a Kirsten Rat Sarcoma (KRAS) gene mutation).
  • Have measurable disease based on RECIST 1.1. Note: Lesions that appear measurable, but are situated in a previously irradiated area, can be considered measurable (eligible for selection as target lesions) if they have shown documented growth since the completion of radiation.
  • Provided an archival tumor tissue sample or newly obtained 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 intervention but before randomization.
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  • Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
  • Male participants must agree for at least 7 days after the last dose of lenvatinib/matching placebo and up to 180 days after the last dose of chemotherapeutic agents to:
  • Refrain from donating sperm PLUS either:
  • Be abstinence from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
  • Must agree to use contraception unless confirmed to be azoopsermic (vasectomized or secondary to medical cause) as detailed below:
  • Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
  • Note: 7 days after lenvatinib/matching placebo is stopped, if the participant is on pembrolizumab only and is greater than 180 days post chemotherapy, no male contraception measures are needed.
  • Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Is not a WOCBP OR
  • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab and/or 30 days post-lenvatinib/matching placebo, and up to 180 days post last dose of chemotherapeutic agents, whichever occurs last.
  • Adequate organ function.
  • Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week prior to randomization. Note: Participants must not have a history of uncontrolled or poorly-controlled hypertension, defined as >150/90 mm Hg for >4 weeks despite standard medical management.

Who cannot join

  • Known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, clinically stable, and have not required steroids for at least 14 days prior to the first dose of study intervention.
  • History of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
  • Radiographic evidence of intratumoral caviations, encasement, or invasion of a major blood vessel. Additionally, the degree of proximity to major blood vessels should be considered for exclusion because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib-therapy. (In the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta).
  • Known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy. Note: The time requirement also does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
  • Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
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  • Has had allogeneic tissue/solid organ transplant.
  • Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority.
  • Known history of Hepatitis B or active Hepatitis C. No testing for Hepatitis B or Hepatitis C is required unless mandated by the local health authority.
  • History of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral drug absorption.
  • Active hemoptysis (at least 0.5 teaspoon of bright red blood) within 2 weeks prior to the first dose of study intervention.
  • Significant cardiovascular impairment within 12 months prior to the first dose of study intervention, including history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA)/stroke, or cardiac arrhythmia associated with hemodynamic instability.
  • Known history of active tuberculosis.
  • Active infection requiring systemic therapy.
  • Has not recovered adequately from any toxicity and/or complication from major surgery prior to the first dose of study intervention.
  • Previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of lenvatinib or pembrolizumab, or as applicable, carboplatin, cisplatin, or pemetrexed.
  • A WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
  • Received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC. Note: 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.
  • Received prior treatment with pembrolizumab or any other anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2 agent, with lenvatinib or any other receptor tyrosine kinase inhibitor (RTKi), or with an agent directed to another stimulatory or co-inhibitory T cell receptor.
  • Received radiotherapy within 14 days prior to the first dose of study intervention or received lung radiation therapy of >30 Gy within 6 months prior to the first dose of study intervention. Note: Participants must have recovered from all radiation-related toxicities to Grade ≤1, not required corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  • Received systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of study intervention.
  • Received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: killed vaccines are allowed.
  • Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study intervention.
  • Has a prolongation of QTc interval (calculated using Fridericia's formula) of >480 msecl.
  • Left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).
  • Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula

Trial locations and contacts

158 sites in 17 countries.

158 sites in 17 countries

China19 sites

  • Peking Union Medical College Hospital ( Site 0108)

    Beijing, Beijing Municipality, 100006

  • Cancer Hospital Chinese Academy of Medical Science ( Site 0117)

    Beijing, Beijing Municipality, 100021

  • Beijing Cancer Hospital ( Site 0120)

    Beijing, Beijing Municipality, 100036

  • Jilin Cancer Hospital ( Site 0115)

    Changchun, Jilin, 130103

  • The Second Hospital Affiliated to AMU ( Site 0119)

    Chongqing, Chongqing Municipality, 400037

  • First Affiliated Hospital of The Third Military Medical University ( Site 0118)

    Chongqing, Chongqing Municipality, 400038

  • Fujian Provincial Cancer Hospital ( Site 0102)

    Fuzhou, Fujian, 350014

  • Southern Medical University Nanfang Hospital ( Site 0121)

    Guangzhou, Guangdong, 510515

  • The First Affiliated Hospital Zhejiang University ( Site 0109)

    Hangzhou, Zhejiang, 310003

  • Zhejiang Cancer Hospital ( Site 0113)

    Hangzhou, Zhejiang, 310022

  • The Third Affiliated Hospital of Harbin Medical University ( Site 0100)

    Harbin, Heilongjiang, 150081

  • Zhongshan Hospital Fudan University ( Site 0103)

    Shanghai, Shanghai Municipality, 200032

  • Shanghai Pulmonary Hospital ( Site 0101)

    Shanghai, Shanghai Municipality, 200443

  • Tianjin Medical University Cancer Institute & Hospital ( Site 0111)

    Tianjin, Tianjin Municipality, 300060

  • Cancer Hospital Affiliated to Xinjiang Medical University ( Site 0110)

    Urumuqi, Xinjiang, 830000

  • The First Affiliated Hospital of Wenzhou Medical University ( Site 0124)

    Wenzhou, Zhejiang, 325000

  • Wuhan Union Hospital Cancer Center-Cancer Center ( Site 0123)

    Wuhan, Hubei, 430022

  • Hubei Cancer Hospital ( Site 0122)

    Wuhan, Hubei, 430079

  • Henan Cancer Hospital ( Site 0112)

    Zhengzhou, Henan, 450008

Other trials in China

United States17 sites

  • Good Samaritan Hospital Corvallis ( Site 0521)

    Corvallis, Oregon, 97330

  • Parkland Health & Hospital System ( Site 0576)

    Dallas, Texas, 75235

  • UT Southwestern Medical Center ( Site 0558)

    Dallas, Texas, 75390

  • Henry Ford Health System ( Site 0563)

    Detroit, Michigan, 48202

  • Sanford Health Roger Maris Cancer Center ( Site 0533)

    Fargo, North Dakota, 58122

  • Holy Cross Hospital ( Site 0512)

    Fort Lauderdale, Florida, 33308

  • West Cancer Center - East Campus ( Site 0544)

    Germantown, Tennessee, 38138

  • Broome Oncology, LLC ( Site 0562)

    Johnson City, New York, 13790

  • Saint Lukes Cancer Institute ( Site 0541)

    Kansas City, Missouri, 64111

  • West Virginia University ( Site 0526)

    Morgantown, West Virginia, 26506

  • El Camino Hospital Cancer Center ( Site 0529)

    Mountain View, California, 94040

  • Yale University ( Site 0519)

    New Haven, Connecticut, 06520-8028

  • Stephenson Cancer Center ( Site 0504)

    Oklahoma City, Oklahoma, 73104

  • Mercy Health-Paducah Medical Oncology and Hematology ( Site 0570)

    Paducah, Kentucky, 42003

  • Thomas Jefferson University Hospital ( Site 0548)

    Philadelphia, Pennsylvania, 19107

  • Utah Cancer Specialists ( Site 0523)

    Salt Lake City, Utah, 84106

  • Abington Hospital - Asplundh Cancer Center ( Site 0575)

    Willow Grove, Pennsylvania, 19090

Other trials in United States

Spain12 sites

  • Complejo Hospitalario Universitario A Coruna ( Site 0239)

    A Coruña, La Coruna, 15006

  • Hospital General Universitario de Alicante ( Site 0240)

    Alicante, 03010

  • Hospital Santa Creu i Sant Pau ( Site 0241)

    Barcelona, 08025

  • ICO L Hospitalet ( Site 0234)

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Hospital Universitario Insular de Gran Canaria ( Site 0244)

    Las Palmas de Gran Canaria, Las Palmas, 35001

  • Hospital General Universitario Gregorio Maranon ( Site 0237)

    Madrid, 28009

  • Hospital Clinico San Carlos ( Site 0235)

    Madrid, 28040

  • Hospital Universitario La Paz ( Site 0236)

    Madrid, 28046

  • Complejo Hospitalario de Malaga ( Site 0238)

    Málaga, 29010

  • Hospital General Universitario de Valencia ( Site 0231)

    Valencia, Valenciana, Comunitat, 46014

  • Hospital Universitario La Fe ( Site 0233)

    Valencia, Valenciana, Comunitat, 46026

  • Hospital Universitario Miguel Servet ( Site 0242)

    Zaragoza, 50009

Other trials in Spain

Japan11 sites

  • Osaka Habikino Medical Center ( Site 0020)

    Habikino, Osaka, 583-8588

  • Kansai Medical University Hospital ( Site 0022)

    Hirakata, Osaka, 573-1191

  • Kanazawa University Hospital ( Site 0018)

    Kanazawa, Ishikawa-ken, 920-8641

  • National Cancer Center Hospital East ( Site 0024)

    Kashiwa, Chiba, 277-8577

  • National Hospital Organization Nagoya Medical Center ( Site 0017)

    Nagoya, Aichi-ken, 460-0001

  • Niigata Cancer Center Hospital ( Site 0019)

    Niigata, 951-8566

  • National Cancer Center Hospital ( Site 0026)

    Tokyo, 104-0045

  • Tokyo Metropolitan Komagome Hospital ( Site 0015)

    Tokyo, 113-8677

  • The Cancer Institute Hospital of JFCR ( Site 0021)

    Tokyo, 135-8550

  • Fujita Health University Hospital ( Site 0016)

    Toyoake, Aichi-ken, 470-1192

  • Wakayama Medical University Hospital ( Site 0025)

    Wakayama, 641-8510

Other trials in Japan

Russia11 sites

  • Moscow Regional Oncological Dispensary ( Site 0274)

    Balashikha, Moscow Oblast, 143900

  • SAHI Republican Clinical Oncological Dispensary of the MoH of RT ( Site 0261)

    Kazan', Tatarstan, Respublika, 420029

  • City Clinical Hospital 1 na. NI. Pirogov ( Site 0270)

    Moscow, Moscow, 119049

  • Central Clinical Hospital with outpatient Clinic ( Site 0262)

    Moscow, Moscow, 121359

  • National Medical Research Radiology Centre ( Site 0260)

    Moscow, Moscow, 125284

  • FSAI Treatment and Rehabilitation Centre of the MoH and SD of RF ( Site 0264)

    Moscow, Moscow, 125367

  • Nizhniy Novgorod Region Oncology Dispensary ( Site 0272)

    Nizhny Novgorod, Nizhny Novgorod Oblast, 603081

  • Omsk Clinical Oncology Dispensary ( Site 0267)

    Omsk, Omsk Oblast, 644013

  • Leningrad Regional Oncology Center ( Site 0271)

    Saint Petersburg, Leningradskaya Oblast', 197758

  • First Pavlov State Medical University of Saint Petersburg-Department of Oncology ( Site 0273)

    Saint Petersburg, Sankt-Peterburg, 197022

  • Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0269)

    Saint Petersburg, Sankt-Peterburg, 197758

Other trials in Russia

United Kingdom10 sites

  • Aberdeen Royal Infirmary ( Site 0288)

    Aberdeen, Scotland, AB25 2ZN

  • Cambridge University Hospitals NHS Trust ( Site 0293)

    Cambridge, Cambridgeshire, CB2 0QQ

  • Leeds Teaching Hospital NHS Trust. St. James University Hospital ( Site 0276)

    Leeds, LS9 7TF

  • Leicester Royal Infirmary ( Site 0284)

    Leicester, LE1 5WW

  • North Middlesex University Hospital NHS Trust ( Site 0291)

    London, London, City of, N18 1QX

  • Guys and St Thomas NHS Foundation Trust ( Site 0280)

    London, London, City of, SE1 9RT

  • St Georges University Hospitals NHS Foundation Trust. ( Site 0292)

    London, London, City of, SW17 0QT

  • Christie NHS Foundation Trust ( Site 0275)

    Manchester, M20 4BX

  • The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0286)

    Metropolitan Borough of Wirral, CH63 4JY

  • Nottingham City Hospital Campus ( Site 0287)

    Nottingham, NG5 1PB

Other trials in United Kingdom

Canada9 sites

  • Juravinski Cancer Centre ( Site 0407)

    Hamilton, Ontario, L8V 1C3

  • Kingston Health Sciences Centre ( Site 0414)

    Kingston, Ontario, K7L 2V7

  • Hopital Cite de la Sante de Laval ( Site 0400)

    Laval, Quebec, H7M 3L9

  • Moncton Hospital - Horizon Health Network ( Site 0410)

    Moncton, New Brunswick, E1C 6Z8

  • CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0412)

    Montreal, Quebec, H3T 1M5

  • Lakeridge Health ( Site 0406)

    Oshawa, Ontario, L1G 2B9

  • CHU de Quebec-Universite Laval-Hotel Dieu de Quebec ( Site 0403)

    Québec, Quebec, G1R 2J6

  • Sault Area Hospital ( Site 0413)

    Sault Ste. Marie, Ontario, P6B 0A8

  • CIUSSS de la Mauricie et du Centre du Quebec ( Site 0408)

    Trois-Rivières, Quebec, G8Z 3R9

Other trials in Canada

France9 sites

  • Hopital Cardiologique Louis Pradel ( Site 0141)

    Bron, Auvergne-Rhône-Alpes, 69500

  • Hopital Nord du Marseille ( Site 0147)

    Marseille, Bouches-du-Rhone, 13015

  • Centre de Cancerologie du Grand Montpellier ( Site 0142)

    Montpellier, Herault, 34070

  • Hopital Laennec ( Site 0146)

    Nantes, Loire-Atlantique, 44093

  • Hopital Cochin ( Site 0140)

    Paris, 75014

  • Centre Paul Strauss ( Site 0144)

    Strasbourg, Bas-Rhin, 67065

  • Hopital Foch ( Site 0145)

    Suresnes, Hauts-de-Seine, 92151

  • Hopital Robert Schuman ( Site 0143)

    Vantoux, Moselle, 57070

  • L'hopital Nord-Ouest - Centre Hospitalier de Villefranche sur Saone ( Site 0149)

    Villefranche-sur-Saône, Rhone, 69655

Other trials in France

Israel9 sites

  • Soroka Medical Center ( Site 0222)

    Beersheba, 8410101

  • Rambam Medical Center ( Site 0223)

    Haifa, 3109601

  • Shaare Zedek Medical Center-Oncology ( Site 0229)

    Jerusalem, 9013102

  • Meir Medical Center ( Site 0221)

    Kfar Saba, 4428164

  • Holy Family Hospital ( Site 0228)

    Nazareth, 1641101

  • Rabin Medical Center ( Site 0224)

    Petah Tikva, 4941492

  • Sheba Medical Center ( Site 0220)

    Ramat Gan, 5262000

  • Sourasky Medical Center ( Site 0225)

    Tel Aviv, 6423906

  • Shamir Medical Center-Assaf Harofeh ( Site 0227)

    Tsrifin, 70300

Other trials in Israel

Argentina8 sites

  • Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0367)

    Berazategui, Buenos Aires, B1884BBF

  • CEMIC ( Site 0370)

    Buenos Aires, Buenos Aires F.D., C1431FWO

  • Hospital Aleman ( Site 0368)

    Buenos Aires, C1118AAT

  • Instituto Medico Especializado Alexander Fleming ( Site 0369)

    Buenos Aires, C1426ANZ

  • CEMAIC ( Site 0374)

    Córdoba, X5008HHW

  • Instituto de Investigaciones Clinicas Mar del Plata ( Site 0371)

    Mar del Plata, Buenos Aires, B7600FZO

  • Sanatorio Parque ( Site 0365)

    Rosario, Santa Fe Province, S2000DSV

  • CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica ( Site 0372)

    San Juan, J5402DIL

Other trials in Argentina

Chile8 sites

  • Centro Oncologico Antofagasta ( Site 0386)

    Antofagasta, 1240000

  • OrlandiOncologia ( Site 0381)

    Santiago, Region M. de Santiago, 7500713

  • Fundacion Arturo Lopez Perez FALP ( Site 0383)

    Santiago, Region M. de Santiago, 7500921

  • Pontificia Universidad Catolica de Chile ( Site 0382)

    Santiago, Region M. de Santiago, 8330032

  • Bradford Hill Centro de Investigaciones Clinicas ( Site 0387)

    Santiago, Region M. de Santiago, 8420383

  • Clinica Universidad Catolica del Maule ( Site 0385)

    Talca, Maule Region, 3465584

  • Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 0380)

    Temuco, Araucania, 4810218

  • Oncocentro ( Site 0384)

    Viña del Mar, Valparaiso, 2520598

Other trials in Chile

Germany8 sites

  • Uniklinik RWTH Aachen ( Site 0160)

    Aachen, North Rhine-Westphalia, 52074

  • Klinikum Esslingen GmbH ( Site 0164)

    Esslingen am Neckar, Baden-Wurttemberg, 73730

  • Krankenhaus Nordwest ( Site 0169)

    Frankfurt am Main, Hesse, 60488

  • LungenClinic Grosshansdorf GmbH ( Site 0171)

    Großhansdorf, Schleswig-Holstein, 22927

  • Krankenhaus Martha Maria Halle-Doelau ( Site 0166)

    Halle, Saxony-Anhalt, 06120

  • Hamato-Onkologie Hamburg Prof. Laack und Partner ( Site 0161)

    Hamburg, 20251

  • Universitaetsklinikum des Saarlandes ( Site 0165)

    Homburg, Saarland, 66421

  • Pius Hospital Oldenburg ( Site 0170)

    Oldenburg, Lower Saxony, 26121

Other trials in Germany

Turkey (Türkiye)8 sites

  • Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi ( Site 0314)

    Adana, 01330

  • Hacettepe Universitesi Tıp Fakultesi ( Site 0316)

    Ankara, 06100

  • Ankara Universitesi Tip Fakultesi. ( Site 0317)

    Ankara, 06620

  • Ankara Sehir Hastanesi ( Site 0323)

    Ankara, 06800

  • Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0312)

    Istanbul, 34098

  • Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0310)

    Istanbul, 34722

  • Ege Universitesi Tip Fakultesi ( Site 0313)

    Izmir, 35100

  • Inonu Universitesi Medical Fakultesi ( Site 0318)

    Malatya, 44280

Other trials in Turkey (Türkiye)

Australia7 sites

  • Ballarat Health Services ( Site 0003)

    Ballarat, Victoria, 3350

  • Blacktown Hospital Western Sydney Local Health District ( Site 0008)

    Blacktown, New South Wales, 2148

  • Cairns Hospital ( Site 0002)

    Cairns, Queensland, 4870

  • The Prince Charles Hospital ( Site 0010)

    Chermside, Queensland, 4032

  • Port Macquarie Base Hospital ( Site 0001)

    Port Macquarie, New South Wales, 2444

  • Chris OBrien Lifehouse ( Site 0006)

    Sydney, New South Wales, 2050

  • Westmead Hospital ( Site 0009)

    Sydney, New South Wales, 2145

Other trials in Australia

Poland6 sites

  • Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 0601)

    Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796

  • Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0602)

    Koszalin, West Pomeranian Voivodeship, 75-581

  • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii ( Site 0613)

    Lodz, Łódź Voivodeship, 93-513

  • Pleszewskie Centrum Medyczne w Pleszewie Sp. z o.o. ( Site 0615)

    Pleszew, Greater Poland Voivodeship, 63-300

  • MED-POLONIA Sp. z o.o. ( Site 0609)

    Poznan, Greater Poland Voivodeship, 60-693

  • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0603)

    Warsaw, Masovian Voivodeship, 02-781

Other trials in Poland

South Korea4 sites

  • Chungbuk National University Hospital ( Site 0062)

    Cheongju-si, North Chungcheong, 28644

  • National Cancer Center ( Site 0061)

    Goyang-si, Kyonggi-do, 10408

  • The Catholic University of Korea St. Vincent s Hospital ( Site 0064)

    Gyeonggi-do, Kyonggi-do, 16247

  • Severance Hospital Yonsei University Health System ( Site 0063)

    Seoul, 03722

Other trials in South Korea

New Zealand2 sites

  • Auckland City Hospital ( Site 0011)

    Auckland, 1023

  • Tauranga Hospital ( Site 0004)

    Tauranga, Bay of Plenty, 3112

Other trials in New Zealand

About this study

Official title: A Phase 3 Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First-line Intervention in Participants With Metastatic Nonsquamous Non-small Cell Lung Cancer (LEAP-006)

The purpose of this study is to assess the safety and efficacy of pemetrexed + platinum chemotherapy + pembrolizumab (MK-3475) with or without lenvatinib (MK-7902/E7080) as first-line intervention in adults with metastatic nonsquamous non-small cell lung cancer.

The primary study hypotheses state that: 1) the combination of lenvatinib + platinum doublet chemotherapy + pembrolizumab prolongs Progression-free Survival (PFS) as assessed by blinded independent central review (BICR) per modified Response Evaluation Criteria in Solid Tumors version 1.1 (RESIST 1.1) compared to matching placebo + platinum doublet chemotherapy + pembrolizumab, and 2) the combination of lenvatinib + platinum doublet chemotherapy + pembrolizumab prolongs Overall Survival (OS) compared to matching placebo + platinum doublet chemotherapy + pembrolizumab.

Keywords
programmed cell death 1 (PD-1, PD1), programmed cell death-ligand 1 (PD-L1, PDL1), programmed cell death-ligand 2 (PD-L2, PDL2)
Medical subject headings
Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

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

Study groups in NCT03829319
Study groupRoleWhat they receive
Pemetrexed+Platinum Chemotherapy+Pembrolizumab+LenvatinibExperimentalParticipants receive carboplatin Area Under Curve 5 mg/mL/min (AUC5) or cisplatin 75 mg/m^2 via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for 4 cycles PLUS pemetrexed 500 mg/m^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS lenvatinib via oral capsule once daily.
Receives: Biological: Pembrolizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Lenvatinib
Pemetrexed+Platinum Chemotherapy+Pembrolizumab+PlaceboPlacebo comparatorIn Parts 1 and 2: Participants receive carboplatin AUC5 or cisplatin 75 mg/m^2 via IV infusion Q3W for 4 cycles PLUS pemetrexed 500 mg/m^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS (Part 2 only) placebo matching lenvatinib via oral capsule once daily.
Receives: Biological: Pembrolizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Placebo matching lenvatinib

What is being measured

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

  1. Part 1: Number of Participants With a Dose-limiting Toxicity (DLT)

    Dose-limiting toxicity using Common Terminology Criteria for Adverse Events v4.0 for grading, is defined as any of the following hematologic toxicities: 1) Grade 4 neutropenia, 2) Grade 3 or 4 febrile neutropenia, 3) thrombocytopenia <25,000 cells/mm^3 associated with bleeding and/or which requires platelet transfusion, or any of the following non-hematologic toxicities: 4) any other Grade 4 or 5 toxicity, 5) Grade 3 toxicities lasting >3 days (exclusions apply), 6) Grade 3 hypertension not controlled by medication, 7) Grade 3 or above gastrointestinal perforation, 8) Grade 3 or above wound dehiscence requiring medical or surgical intervention, 9) any grade thromboembolic event, or 10) any Grade 3 nonhematologic laboratory value if medical intervention is required or the abnormality leads to hospitalization.

    Measured: Cycle 1; each cycle is 21 days (up to 21 days)

  2. Part 1: Number of Participants Who Experienced an Adverse Event (AE)

    An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience one of more adverse events during Part 1 of this study will be presented.

    Measured: Up to approximately 48 months

  3. Part 1: Number of Participants Who Discontinued Study Drug Due to an Adverse Event

    An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study medication due to and adverse event during Part 1 of this study will be presented.

    Measured: Up to approximately 58 months

  4. Part 2: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    PFS was defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥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 ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Data are from the product-limit (Kaplan-Meier) method for censored data. PFS as assessed by blinded independent central review (BICR) per RECIST 1.1 is presented.

    Measured: Up to approximately 36 months

  5. Part 2: Overall Survival (OS)

    OS is defined as the time from randomization to the time of death from any cause. OS is presented.

    Measured: Up to approximately 47 months

Secondary outcomes (15)

  1. Part 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    ORR is defined as the percentage of participants in the analysis population who have 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) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR as assessed per modified RECIST 1.1 will be presented.

    Measured: Up to approximately 19 months

  2. Part 2: Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until PD or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, or death from any cause, PD is defined as ≥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 ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. DOR as assessed per modified RECIST 1.1 will be presented.

    Measured: Up to approximately 48 months

  3. Part 2: Number of Participants Who Experienced an Adverse Event (AE)

    An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced one of more adverse events during Part 2 of this study were presented.

    Measured: Up to approximately 58 months

  4. Part 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event

    An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study treatment during Part 2 of this study were presented.

    Measured: Up to approximately 58 months

  5. Part 2: Change From Baseline in Global Health Status (GHS) (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] Items 29 and 30) 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 27

  6. Part 2: Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score

    The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in cough (EORTC QLQ-LC13 Item 31) score will be presented. A lower score indicates a better outcome.

    Measured: Baseline and week 27

  7. Part 2: Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score

    The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score will be presented. A lower score indicates a better outcome.

    Measured: Baseline and Week 27

  8. Part 2: Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score

    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score will be presented. A lower score indicates a better outcome.

    Measured: Baseline and Week 27

  9. Part 2: Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score

    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented. A higher score indicates a better quality of life.

    Measured: Baseline and Week 27

  10. Part 2: Time to True Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS)/Quality of Life (QoL) (EORTC QLQ-C30 Items 29 and 30) Score

    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in GHS/QoL (EORTC QLQ-C30 Items 29 and 30) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from Baseline in GHS/QoL score, will be presented. A longer TTD indicates a better outcome.

    Measured: Baseline and Week 27

  11. Part 2: TTD Based on Change From Baseline in Cough EORTC QLQ-LC13 (Item 31) Score

    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline cough (EORTC QLQ-LC30 Items 31) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from Baseline in physical functioning score, will be presented. A longer TTD indicates a better outcome.

    Measured: Baseline And Week 27

  12. Part 2: TTD Based on Change From Baseline in Chest Pain EORTC QLQ-LC13 (Item 40) Score

    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline chest pain (EORTC QLQ-C30 Item 40) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from Baseline in chest pains core, will be presented. A longer TTD indicates a better outcome.

    Measured: Baseline and Week 27

  13. Part 2: TTD Based on Change From Baseline in Dyspnea EORTC QLQ-C30 (Item 8) Score

    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline dyspnea (EORTC QLQ-C30 Item 8) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from Baseline in dyspnea score, will be presented. A longer TTD indicates a better outcome.

    Measured: Baseline and Week 27

  14. Part 2: TTD Based on Change From Baseline in Physical Functioning EORTC QLQ-C30 (Items 1 Through 5) Score

    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline physical functioning (EORTC QLQ-C30 Items 1 through 5) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from Baseline in physical functioning score, will be presented. A longer TTD indicates a better outcome.

    Measured: Baseline and Week 27

  15. Part 2: Time to True Deterioration (TTD) Based on Change From Baseline in the Composite Endpoint of Cough (EORTC QLQ-LC13 Item 31), Chest Pain (EORTC QLQ-LC13 Item 40), or Dyspnea (EORTC QLQ-C30 Item 8)

    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in the composite endpoint of cough (QLQ-LC13 item 31), chest pain (QLQ-LC13 item 40), or dyspnea (QLQ-C30 Item 8). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from Baseline in the composite endpoint of cough, chest pain or dyspnea, will be presented. A longer TTD indicates a better outcome.

    Measured: Baseline and Week 27

Timeline

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

  1. First posted4 Feb 2019
  2. Study start25 Mar 2019
  3. Primary completion11 Aug 2023
  4. Study completion30 Aug 2024

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
Double blind
Who is masked
Participant, Investigator
Enrolment
761 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03829319
Sponsor's protocol ID
7902-006
Other IDs
MK-7902-006, E7080-G000-315, LEAP-006, 194658, 2018-003824-35, 2018
Status last verified
Dec 2025
First submitted
1 Feb 2019
Last updated
5 Feb 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Herbst RS, Cho BC, Zhou C, Burotto M, Dols MC, Sendur MAN, Moiseyenko V, Casarini I, Nishio M, Hui R, Pons-Tostivint E, Dudnik J, Ahmed S, Okpara CE, Dutcus C, Yin L, Luo Y, Chirovsky D, Bhagwati N, Abreu DR. Lenvatinib Plus Pembrolizumab, Pemetrexed, and a Platinum as First-Line Therapy for Metastatic Nonsquamous NSCLC: Phase 3 LEAP-006 Study. J Thorac Oncol. 2025 Sep;20(9):1302-1314. doi: 10.1016/j.jtho.2025.05.016. Epub 2025 May 24.

    PubMed 40419140

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab, Carboplatin and Cisplatin in people with Nonsquamous 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 19 inclusion and 27 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 5 Feb 2026. 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, Spain, Japan, Russia 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. Some participants in this study may receive a placebo. 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 21 Feb 2025). 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?

Part 1: Number of Participants With a Dose-limiting Toxicity (DLT) (time frame: Cycle 1; each cycle is 21 days (up to 21 days)). The study lists 5 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 NCT03829319, 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 5 Feb 2026.

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