Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) in Adults With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Treatment-naïve Nonsmall Cell Lung Cancer (NSCLC) (MK-7902-007/E7080-G000-314/LEAP-007)

A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) in Participants With Treatment-naïve, Metastatic Nonsmall Cell Lung Cancer (NSCLC) Whose Tumors Have a Tumor Proportion Score (TPS) Greater Than or Equal to 1% (LEAP-007)

The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) in treatment-naïve adults with no prior systemic therapy for their metastatic non-small cell lung cancer (NSCLC) whose tumors have a programmed cell death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) greater than or equal to 1%.

The primary study hypotheses are that: 1) the combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1); and 2) the combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Overall Survival (OS).

Study Overview

• Status: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Biological: Pembrolizumab; Drug: Lenvatinib; Drug: Placebo for lenvatinib

Detailed Description

As of 30-Jul-2021, active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded. Participants will discontinue lenvatinib and placebo, and participants who remain on treatment will receive open-label pembrolizumab only.

• Study Type: Interventional
• Enrollment (Actual): 623
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Orange, New South Wales, Australia, 2800
      • Orange Health Services ( Site 0002)
    • Wollongong, New South Wales, Australia, 2500
      • Wollongong Private Hospital ( Site 0005)
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • The Prince Charles Hospital ( Site 0011)
  • Victoria
    • Wendouree, Victoria, Australia, 3355
      • Ballarat Oncology and Haematology Services ( Site 0008)
  • Western Australia
    • Perth, Western Australia, Australia, 6150
      • St John of God Murdoch Medical Clinic ( Site 0001)
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute ( Site 0400)
  • British Columbia
    • North Vancouver, British Columbia, Canada, V7L 2L7
      • Lions Gate Hospital ( Site 0407)
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • William Osler Health System (Brampton Civic Hospital) ( Site 0402)
    • Windsor, Ontario, Canada, N8W 2X3
      • Windsor Regional Cancer Program ( Site 0404)
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre ( Site 0418)
• China
  • Anhui
    • Beijing, Anhui, China, 101149
      • Beijing Chest Hospital Capital Medical University ( Site 0111)
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Hospital ( Site 0108)
    • Hefei, Anhui, China, 230088
      • The First Affiliated Hospital of Anhui Medical University ( Site 0113)
  • Beijing
    • Beijing, Beijing, China, 100006
      • Peking Union Medical College Hospital ( Site 0105)
    • Beijing, Beijing, China, 100036
      • Beijing Cancer Hospital ( Site 0102)
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Central South University ( Site 0115)
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital ( Site 0104)
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Jiangsu Cancer Hospital ( Site 0101)
  • Jilin
    • Chang chun, Jilin, China, 130021
      • The First Hospital of Jilin University ( Site 0110)
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Zhongshan Hospital Fudan University ( Site 0100)
    • Shanghai, Shanghai, China, 230000
      • Shanghai Chest Hospital ( Site 0112)
  • Shanxi
    • XiAn, Shanxi, China, 710061
      • 1st Affil Hosp of Med College of Xi'an Jiaotong University ( Site 0103)
  • Sichuan
    • Chengdu, Sichuan, China, 510115
      • West China Hospital of Sichuan University ( Site 0117)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital ( Site 0116)
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital Zhejiang University ( Site 0106)
    • Hangzhou, Zhejiang, China, 310006
      • Hangzhou First People's Hospital ( Site 0109)
    • Hangzhou, Zhejiang, China, 310009
      • 2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0114)
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 050015
      • Hospital General de Medellin Luz Castro de Gutierrez ( Site 0368)
    • Medellin, Antioquia, Colombia, 050021
      • Fundacion Centro de Investigacion Clinica CIC ( Site 0366)
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 080002
      • Biomelab S A S ( Site 0365)
  • Cesar
    • Valledupar, Cesar, Colombia, 200001
      • Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0374)
  • Cordoba
    • Monteria, Cordoba, Colombia, 230002
      • Oncomedica S.A. ( Site 0372)
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia, 760023
      • Centro Medico Imbanaco de Cali S.A ( Site 0369)
• Estonia
  • Harjumaa
    • Tallin, Harjumaa, Estonia, 13419
      • SA Pohja-Eesti Regionaalhaigla ( Site 0162)
    • Tallinn, Harjumaa, Estonia, 11312
      • AS Ida-Tallinna Keskhaigla ( Site 0161)
  • Tartumaa
    • Tartu, Tartumaa, Estonia, 50406
      • SA Tartu Ulikooli Kliinikum ( Site 0160)
• France
  • Paris, France, 75248
    • Institut Curie ( Site 0166)
  • Doubs
    • Besancon, Doubs, France, 25000
      • CHU Jean Minjoz ( Site 0167)
  • Hauts-de-Seine
    • Saint-Cloud, Hauts-de-Seine, France, 92210
      • Institut Curie - Centre Rene Huguenin ( Site 0181)
  • Herault
    • Montpellier, Herault, France, 34090
      • ICM Val D Auerelle ( Site 0177)
  • Isere
    • La Tronche, Isere, France, 38700
      • CHU de Grenoble - Hopital Michallon ( Site 0169)
  • Loire-Atlantique
    • Saint Herblain, Loire-Atlantique, France, 44805
      • Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0185)
  • Pyrenees-Atlantiques
    • Bayonne, Pyrenees-Atlantiques, France, 64109
      • Centre Hospitalier de la Cote Basque ( Site 0173)
  • Seine-Maritime
    • Rouen, Seine-Maritime, France, 76000
      • CHU de Rouen ( Site 0174)
  • Somme
    • Amiens, Somme, France, 80054
      • CHU Amiens Sud ( Site 0182)
  • Var
    • Toulon, Var, France, 83056
      • Centre hospitalier Toulon Sainte-Musse ( Site 0172)
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem ( Site 0210)
  • Kaposvar, Hungary, 7400
    • Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0217)
  • Bekes
    • Gyula, Bekes, Hungary, 5700
      • Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 0207)
  • Borsod-Abauj-Zemplen
    • Miskolc, Borsod-Abauj-Zemplen, Hungary, 3529
      • Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz ( Site 0202)
    • Miskolc, Borsod-Abauj-Zemplen, Hungary, 3529
      • CRU Hungary KFT ( Site 0209)
  • Gyor-Moson-Sopron
    • Gyor, Gyor-Moson-Sopron, Hungary, 9024
      • Petz Aladar Megyei Oktato Korhaz ( Site 0213)
  • Jasz-Nagykun-Szolnok
    • Szolnok, Jasz-Nagykun-Szolnok, Hungary, 5000
      • Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0203)
  • Pest
    • Torokbalint, Pest, Hungary, 2045
      • Tudogyogyintezet Torokbalint ( Site 0205)
• Israel
  • Beer Sheva, Israel, 8457108
    • Soroka Medical Center ( Site 0222)
  • Haifa, Israel, 3109601
    • Rambam Medical Center ( Site 0223)
  • Kfar-Saba, Israel, 4428132
    • Meir Medical Center ( Site 0221)
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center ( Site 0224)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 0225)
  • Heifa
    • Haifa, Heifa, Israel, 3339419
      • Bnei Zion Medical Center ( Site 0227)
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 5266202
      • Sheba Medical Center ( Site 0220)
  • Ḥeifā
    • Ashkelon, Ḥeifā, Israel, 7830604
      • Barzilai Medical Center ( Site 0226)
• Italy
  • Avellino, Italy, 83100
    • Azienda Ospedaliera San Giuseppe Moscati ( Site 0234)
  • Catanzaro, Italy, 88100
    • Universita Magna Grecia ( Site 0230)
  • Firenze, Italy, 50134
    • A.O. Universitaria Careggi ( Site 0236)
  • Ravenna, Italy, 48121
    • Ospedale Santa Maria delle Croci ( Site 0232)
  • Roma, Italy, 00168
    • Policlinico Gemelli di Roma ( Site 0237)
  • Lazio
    • Roma, Lazio, Italy, 00185
      • Azienda Ospedaliera S. Giovanni Addolorata-Oncologia Medica ( Site 0233)
  • Messina
    • Taormina, Messina, Italy, 98039
      • Presidio Ospedaliero San Vincenzo ( Site 0231)
  • Pordenone
    • Aviano, Pordenone, Italy, 33081
      • Centro di Riferimento Oncologico CRO ( Site 0235)
• Japan
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center ( Site 0015)
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital ( Site 0030)
  • Okayama, Japan, 700-8558
    • Okayama University Hospital ( Site 0020)
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute ( Site 0019)
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital ( Site 0016)
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital ( Site 0029)
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital ( Site 0024)
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
      • Aichi Cancer Center Hospital ( Site 0018)
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital ( Site 0025)
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
      • Hyogo Cancer Center ( Site 0021)
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 236-0051
      • Kanagawa Cardiovascular and Respiratory Center ( Site 0026)
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center ( Site 0023)
  • Miyagi
    • Natori, Miyagi, Japan, 981-1293
      • Miyagi Cancer Center ( Site 0028)
    • Sendai, Miyagi, Japan, 980-0873
      • Sendai Kousei Hospital ( Site 0022)
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
      • Kindai University Hospital ( Site 0017)
    • Sakai, Osaka, Japan, 591-8555
      • National Hospital Organization Kinki-chuo Chest Medical Center ( Site 0027)
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center ( Site 0076)
  • Seoul, Korea, Republic of, 07061
    • SMG-SNU Boramae Medical Center ( Site 0078)
  • Chungbuk
    • Cheongju si, Chungbuk, Korea, Republic of, 28644
      • Chungbuk National University Hospital ( Site 0079)
  • Kyonggi-do
    • Seongnam-si, Kyonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital ( Site 0075)
  • Ulsan-Kwangyokshi
    • Ulsan, Ulsan-Kwangyokshi, Korea, Republic of, 44033
      • Ulsan University Hospital ( Site 0077)
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre ( Site 0061)
  • Pulau Pinang, Malaysia, 10050
    • Gleneagles Penang ( Site 0066)
  • Pahang
    • Kuantan, Pahang, Malaysia, 25100
      • Hospital Tengku Ampuan Afzan ( Site 0062)
  • Pulau Pinang
    • Georgetown, Pulau Pinang, Malaysia, 10990
      • Hospital Pulau Pinang. ( Site 0065)
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Sarawak General Hospital ( Site 0064)
  • Selangor
    • Petaling Jaya, Selangor, Malaysia, 46050
      • Beacon Hospital Sdn Bhd ( Site 0067)
  • Wilayah Persekutuan Putrajaya
    • Putrajaya, Wilayah Persekutuan Putrajaya, Malaysia, 62250
      • Institut Kanser Negara - National Cancer Institute ( Site 0063)
• Mexico
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Cancerologia. ( Site 0382)
  • Oaxaca, Mexico, 68000
    • Oaxaca Site Management Organization SC ( Site 0389)
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 14050
      • Medica Sur S.A.B de C.V. ( Site 0384)
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44680
      • Consultorios de Medicina Especializada del Sector Privado ( Site 0388)
  • Tamaulipas
    • Madero, Tamaulipas, Mexico, 89440
      • Centro de Estudios de Investigacion Metabolicos y Cardiovasculares ( Site 0381)
• Poland
  • Lodzkie
    • Lodz, Lodzkie, Poland, 99-153
      • SPZOZ USK nr 1 im. Norberta Barlickiego UM w Lodzi ( Site 0256)
  • Lubuskie
    • Zielona Gora, Lubuskie, Poland, 65-046
      • Szpital Uniwersytecki im. Karola Marcinkowskiego ( Site 0247)
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-202
      • Krakowski Szpital Specjalistyczny im Jana Pawla II ( Site 0253)
    • Krakow, Malopolskie, Poland, 31-826
      • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 0243)
  • Mazowieckie
    • Ostroleka, Mazowieckie, Poland, 07-410
      • Centrum Medyczne Pratia Ostroleka ( Site 0242)
    • Warszawa, Mazowieckie, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0252)
  • Podkarpackie
    • Przemysl, Podkarpackie, Poland, 37-700
      • Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 0250)
  • Wielkopolskie
    • Pila, Wielkopolskie, Poland, 64-920
      • Ars Medical Sp. z o.o. ( Site 0254)
• Russian Federation
  • Baskortostan, Respublika
    • Ufa, Baskortostan, Respublika, Russian Federation, 450054
      • Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 0262)
  • Krasnoyarskiy Kray
    • Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation, 660133
      • Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0266)
  • Samarskaya Oblast
    • Samara, Samarskaya Oblast, Russian Federation, 443031
      • SBHI Samara Regional Clinical Oncology Dispensary ( Site 0265)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 194291
      • SBHI Leningrad Regional Clinical Hospital ( Site 0263)
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 195271
      • Railway Hospital of OJSC ( Site 0268)
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 198255
      • City Clinical Oncology Center ( Site 0260)
  • Tatarstan, Respublika
    • Kazan, Tatarstan, Respublika, Russian Federation, 420029
      • Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0269)
• Taiwan
  • Hsinchu, Taiwan, 300
    • National Taiwan University Hospital Hsin-Chu Branch ( Site 0087)
  • New Taipei, Taiwan, 235
    • Taipei Medical University Shuang Ho Hospital ( Site 0090)
  • Tainan, Taiwan, 70457
    • National Cheng Kung University Hospital ( Site 0086)
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital ( Site 0088)
  • Taipei, Taiwan, 112
    • Koo Foundation Sun Yat-Sen Cancer Center ( Site 0091)
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital ( Site 0089)
• Turkey
  • Ankara, Turkey, 06010
    • Gulhane Egitim ve Arastirma Hastanesi ( Site 0316)
  • Ankara, Turkey, 06200
    • Abdurrahman Yurtaslan Onkoloji Hastanesi ( Site 0318)
  • Ankara, Turkey, 06490
    • Baskent Universitesi Ankara Hastanesi ( Site 0319)
  • Antalya, Turkey, 07020
    • Antalya Memorial Hospital Department of Medical Oncology ( Site 0324)
  • Antalya, Turkey, 07070
    • Akdeniz Universitesi Tip Fakultesi ( Site 0322)
  • Izmir, Turkey, 35340
    • Dokuz Eylul Universitesi Arastirma Uygulama Hastanesi ( Site 0314)
  • Sakarya, Turkey, 54290
    • Sakarya Universitesi Egitim ve Arastirma Hastanesi ( Site 0323)
  • Samsun, Turkey, 55200
    • Samsun Medical Park Hastanesi ( Site 0320)
  • Adana
    • Konya, Adana, Turkey, 42080
      • Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 0321)
• Ukraine
  • Cherkaska Oblast
    • Cherkasy, Cherkaska Oblast, Ukraine, 18009
      • Cherkasy Regional Hospital ( Site 0336)
  • Dnipropetrovska Oblast
    • Dnipro, Dnipropetrovska Oblast, Ukraine, 49102
      • City Clinical Hosp.4 of DCC ( Site 0338)
  • Ivano-Frankivska Oblast
    • Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine, 76018
      • MI Precarpathian Clinical Oncology Center ( Site 0346)
  • Kharkivska Oblast
    • Kharkiv, Kharkivska Oblast, Ukraine, 61070
      • Regional Centre of Oncology-Thoracic organs ( Site 0337)
  • Kirovohradska Oblast
    • Kropyvnytskiy, Kirovohradska Oblast, Ukraine, 25011
      • Ukranian Center of TomoTherapy ( Site 0344)
  • Kyivska Oblast
    • Kyiv, Kyivska Oblast, Ukraine, 03039
      • Medical Center Verum ( Site 0334)
    • Kyiv, Kyivska Oblast, Ukraine, 03115
      • Kyiv City Clinical Oncology Centre ( Site 0339)
    • Kyiv, Kyivska Oblast, Ukraine, 03126
      • Medical and Diagnostic Centre LLC Dobryi Prognoz ( Site 0331)
  • Lvivska Oblast
    • Lviv, Lvivska Oblast, Ukraine, 79031
      • Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 0341)
  • Odeska Oblast
    • Odesa, Odeska Oblast, Ukraine, 65055
      • MI Odessa Regional Oncological Centre ( Site 0333)
  • Vinnytska Oblast
    • Vinnytsia, Vinnytska Oblast, Ukraine, 21029
      • Podillya Regional Center of Oncology ( Site 0343)
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99503
      • Alaska Clinical Research Center ( Site 0511)
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer & Research Centers ( Site 0541)
  • California
    • Bakersfield, California, United States, 93309
      • CBCC Global Research, Inc. ( Site 0532)
    • La Jolla, California, United States, 92037
      • Scripps Cancer Center ( Site 0521)
  • Florida
    • Orlando, Florida, United States, 32803
      • Florida Hospital ( Site 0526)
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers PC ( Site 0518)
  • Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois Cancer Care, PC ( Site 0557)
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Parkview Cancer Center ( Site 0542)
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky School of Medicine & Hospitals ( Site 0517)
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Medical Center Oncology and Hematology ( Site 0514)
  • Michigan
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center ( Site 0512)
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55426
      • Park Nicollet Frauenshuh Cancer Center ( Site 0554)
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri Health Care ( Site 0555)
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center ( Site 0508)
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • Cone Health Cancer Center at Alamance Regional ( Site 0527)
  • Ohio
    • Zanesville, Ohio, United States, 43701
      • Genesis Cancer Care Center ( Site 0559)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University ( Site 0544)
  • Texas
    • Temple, Texas, United States, 76504
      • Central Texas Veterans Healthcare System ( Site 0533)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Has a histologically or cytologically confirmed diagnosis of NSCLC.
• Has Stage IV NSCLC (American Joint Committee on Cancer [AJCC 8th edition]).
• Has measurable disease based on RECIST 1.1.
• Has tumor tissue that demonstrates programmed cell death-ligand 1 (PD-L1) expression in ≥1% of tumor cells (Tumor Proportion Score [TPS] ≥1%) as assessed by immunohistochemistry (IHC) 22C3 pharmDx assay (Dako North America, Inc.) at a central laboratory.
• Has a life expectancy of ≥3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study treatment but before randomization.
• Male participants must agree to the following during the treatment period and for ≥7 days after the last dose of lenvatinib/matching placebo: 1) Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR 2) Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause).
• Female participants are eligible to participate if not pregnant or breastfeeding, and ≥1 of the following applies: 1) Is not a woman of child-bearing potential (WOCBP), OR 2) Is a WOCBP and is using a highly effective contraceptive method that has a low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle during the treatment period and for ≥120 days post pembrolizumab or ≥30 days post lenvatinib/matching placebo, whichever occurs last.
• Has 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 before randomization.
• Has adequate organ function.

Exclusion Criteria:

• Has known untreated central nervous system metastases and/or carcinomatous meningitis.
• Has active hemoptysis (at least 0.5 teaspoon of bright red blood) within 2 weeks prior to the first dose of study intervention.
• Has radiographic evidence of intratumoral cavitations, encasement, or invasion of a major blood vessel.
• Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for ≥3 years since initiation of that therapy. (Note: The time requirement 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.)
• Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has had an allogeneic tissue/solid organ transplant.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
• Has a known history of hepatitis B or known active hepatitis C virus infection.
• Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral study drug absorption.
• Has significant cardiovascular impairment within 12 months of the first dose of study treatment, such as a history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident/stroke, or cardiac arrhythmia associated with hemodynamic instability.
• Has not recovered adequately from any toxicity and/or complications from major surgery before starting study treatment.
• Has a known history of active tuberculosis (TB).
• Has an active infection requiring systemic therapy.
• Has previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity or intolerance to any component of lenvatinib or pembrolizumab.
• Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC.
• Has received prior therapy with an anti-PD-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], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137]) or has received lenvatinib as monotherapy or in combination with anti- programmed cell death protein (anti-PD-1) agents.
• Has received radiotherapy within 14 days before the first dose of study treatment or received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment. (Note: Participants must have recovered from all radiation-related toxicities to ≤Grade 1, not require corticosteroids, and not have had radiation pneumonitis.)
• Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days before the first dose of study treatment.
• Is receiving systemic steroid therapy (doses >10 mg daily of prednisone equivalent) within 7 days before the first dose of study treatment.
• Has received a live or attenuated vaccine within 30 days before the first dose of study treatment.
• Has had major surgery within 3 weeks prior to first dose of study treatment
• Has pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab + Lenvatinib; Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Lenvatinib; oral capsule; Other Names: E7080; MK-7902; LENVIMA®
Active Comparator: Pembrolizumab + Placebo; Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Placebo for lenvatinib; oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) as Assessed by 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.	Up to approximately 25 months
Overall Survival (OS)	OS was defined as the time from date of randomization to date of death from any cause. OS is presented.	Up to approximately 25 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	ORR was 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. ORR as assessed by BICR per RECIST 1.1 is presented.	Up to approximately 25 months
Number of Participants Who Experience an Adverse Event (AE)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.	Through 90 days post last dose of study treatment (Up to approximately 27 months)
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	The number of participants who discontinue study treatment due to an AE will be presented.	Through last dose of study treatment (Up to approximately 24 months)
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] Item 29) Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "How would you rate your overall health during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) score will be presented. A higher score indicates a better overall GHS.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
Change From Baseline in Quality of Life (QoL) (EORTC QLQ-C30 Item 30) Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question " How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in QoL (EORTC QLQ-C30 Item 30) score will be presented. A higher score indicates a better overall QoL.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
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.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
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.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
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.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
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.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
Time to True Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS) (EORTC QLQ-C30 Item 29) Score	TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in GHS (EORTC QLQ-C30 Item 29) 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 score, will be presented. A longer TTD indicates a better outcome.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
Time to True Deterioration (TTD) Based on Change From Baseline in Quality of Life (QoL) (EORTC QLQ-C30 Item 30) Score	TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in QoL (EORTC QLQ-C30 Item 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 QoL score, will be presented. A longer TTD indicates a better outcome.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
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.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score	TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in physical functioning (EORTC QLQ-C30 Items 1-5) 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.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Eisai Inc.
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Taylor MH, Schmidt EV, Dutcus C, Pinheiro EM, Funahashi Y, Lubiniecki G, Rasco D. The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Future Oncol. 2021 Feb;17(6):637-648. doi: 10.2217/fon-2020-0937. Epub 2020 Dec 10.

Helpful Links

• Merck Clinical Trial Information

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2019
• Primary Completion (Actual): May 19, 2021
• Study Completion (Estimated): April 24, 2024

Study Registration Dates

• First Submitted: February 1, 2019
• First Submitted That Met QC Criteria: February 1, 2019
• First Posted (Actual): February 4, 2019

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: programmed cell death 1 (PD-1, PD1); programmed cell death-ligand 1 (PD-L1, PDL1); programmed cell death-ligand 2 (PD-L2, PDL2)
• 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; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; Pembrolizumab; Lenvatinib
• Other Study ID Numbers: 7902-007; MK-7902-007 (Other Identifier: Merck Protocol Number); E7080-G000-314 (Other Identifier: Eisai Protocol Number); LEAP-007 (Other Identifier: Merck); 194670 (Registry Identifier: JAPIC-CTI); 2018-003794-98 (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