A Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First Line (1L) Intervention in a Programmed Cell Death-ligand 1 (PD-L1) Selected Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (LEAP-010) (MK-7902-010) (LEAP-10)

A Phase 3, Randomized, Placebo-controlled, Double-blind Clinical Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) to Evaluate the Safety and Efficacy of Pembrolizumab and Lenvatinib as 1L Intervention in a PD-L1 Selected Population of Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (LEAP-010).

This is a study of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) as a first line intervention in a PD-L1 selected population with participants with recurrent or metastatic head and neck squamous cell carcinoma.

Hypotheses include:

• Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).
• Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR.
• Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to overall survival (OS).

Study Overview

• Status: Active, not recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Lenvatinib; Drug: Placebo; Biological: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 511
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris OBrien Lifehouse ( Site 1002)
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital ( Site 1001)
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital ( Site 1004)
• Brazil
  • Sao Paulo, Brazil, 01509-900
    • A.C. Camargo Cancer Center ( Site 0407)
  • Ceara
    • Fortaleza, Ceara, Brazil, 60135-237
      • Oncocentro Ceara ( Site 0412)
  • Minas Gerais
    • Ipatinga, Minas Gerais, Brazil, 35162-189
      • Fundacao Sao Francisco Xavier ( Site 0409)
  • Parana
    • Maringa, Parana, Brazil, 87015-200
      • ELO Pesquisa Clinica ( Site 0405)
  • Rio Grande Do Sul
    • Passo Fundo, Rio Grande Do Sul, Brazil, 99010-260
      • Hospital de Passo Fundo ( Site 0401)
    • Pelotas, Rio Grande Do Sul, Brazil, 96020-080
      • Clinica LACKS ( Site 0402)
    • Porto Alegre, Rio Grande Do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 0414)
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Centre ( Site 0200)
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre ( Site 0206)
    • Quebec City, Quebec, Canada, G1J 1Z4
      • Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
• China
  • Beijing
    • Beining, Beijing, China, 100036
      • Beijing Cancer Hospital ( Site 3314)
    • Bejiing, Beijing, China, 100032
      • Peking Union Medical College Hospital ( Site 3304)
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Chongqing Cancer Hospital ( Site 3327)
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Provincial Cancer Hospital ( Site 3326)
  • Guangxi
    • Nanning, Guangxi, China, 530000
      • Guangxi Medical University Affiliated Tumor Hospital ( Site 3322)
  • Guizhou
    • Guiyang, Guizhou, China, 550003
      • Guizhou Cancer Hospital ( Site 3330)
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • The Third Affiliated Hospital of Harbin Medical University ( Site 3302)
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital ( Site 3309)
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Wuhan Union hospital Cancer Center ( Site 3307)
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital Tongji Medical,Science & Technology ( Site 3316)
  • Hunan
    • Changsha, Hunan, China, 410000
      • Hunan Cancer Hospital ( Site 3311)
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Central South University ( Site 3305)
  • Jiangxi
    • Nanchang, Jiangxi, China, 330029
      • Jiangxi Cancer Hospital ( Site 3313)
  • Jilin
    • Changchun, Jilin, China, 130000
      • Jilin Cancer Hospital ( Site 3310)
  • Shaanxi
    • XI An, Shaanxi, China, 710000
      • The First Affiliated Hospital of Xi an Jiaotong University ( Site 3328)
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center ( Site 3324)
    • Shanghai, Shanghai, China, 200120
      • Shanghai East Hospital ( Site 3300)
  • Sichuan
    • Chengdu, Sichuan, China, 610047
      • West China Hospital of Sichuan University ( Site 3308)
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Hospital ( Site 3312)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital ( Site 3303)
• France
  • Auvergne
    • Lyon, Auvergne, France, 69008
      • Centre Leon Berard ( Site 1901)
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13005
      • Hopital de la Timone ( Site 1903)
  • Hauts-de-Seine
    • Suresnes, Hauts-de-Seine, France, 92151
      • Hopital Foch ( Site 1905)
  • Seine-Maritime
    • Rouen, Seine-Maritime, France, 76038
      • Centre Henri Becquerel ( Site 1904)
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94800
      • Gustave Roussy ( Site 1906)
• Germany
  • Berlin, Germany, 12203
    • Charite Universitätsmedizin Berlin Campus Benjamin Franklin ( Site 2112)
  • Baden-Wurttemberg
    • Tuebingen, Baden-Wurttemberg, Germany, 72076
      • Universitaetsklinikum Tuebingen ( Site 2108)
    • Ulm, Baden-Wurttemberg, Germany, 89075
      • Universitaetsklinikum Ulm ( Site 2102)
  • Bayern
    • Regensburg, Bayern, Germany, 93053
      • Universitaetsklinikum Regensburg ( Site 2100)
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • Universitaetsklinikum Frankfurt ( Site 2107)
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30459
      • KRH Klinikum Siloah ( Site 2103)
  • Nordrhein-Westfalen
    • Koeln, Nordrhein-Westfalen, Germany, 50937
      • Universitaetsklinikum Koeln ( Site 2111)
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Universitätsklinikum Leipzig-Department for ENT ( Site 2106)
• Hungary
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet ( Site 2202)
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont ( Site 2206)
  • Borsod-Abauj-Zemplen
    • Miskolc, Borsod-Abauj-Zemplen, Hungary, 3526
      • Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce
  • Csongrad
    • Szeged, Csongrad, Hungary, 6720
      • Szegedi Egyetem Szent-Gyorgyi Albert Klinikai Kozpont ( Site 2207)
  • Jasz-Nagykun-Szolnok
    • Szolnok, Jasz-Nagykun-Szolnok, Hungary, 5004
      • Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 2200)
  • Vas
    • Budapest, Vas, Hungary, 1145
      • Uzsoki Utcai Korhaz ( Site 2201)
• Italy
  • Brescia, Italy, 25123
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia ( Site 2402)
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 2400)
  • Milano, Italy, 20141
    • IEO Istituto Europeo di Oncologia ( Site 2406)
  • Milano, Italy, 20142
    • ASST Santi Paolo e Carlo - Presidio Ospedaliero San Paolo ( Site 2405)
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto ( Site 2404)
  • Savona, Italy, 17100
    • ASL Liguria 2 - Ospedale San Paolo ( Site 2401)
• Japan
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center ( Site 1111)
  • Hiroshima, Japan, 7348551
    • Hiroshima University Hospital ( Site 1109)
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital ( Site 1102)
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of JFCR ( Site 1103)
  • Tokyo, Japan
    • Tokyo Medical and Dental University Hospital ( Site 1101)
  • Aichi
    • Nagoya, Aichi, Japan, 4648681
      • Aichi Cancer Center Hospital ( Site 1113)
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital ( Site 1106)
  • Chiba
    • Chiba-shi, Chiba, Japan, 260-8717
      • Chiba cancer center ( Site 1110)
    • Kashiwa, Chiba, Japan, 2778577
      • National Cancer Center Hospital East ( Site 1100)
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
      • Hyogo Cancer Center ( Site 1112)
  • Kagawa
    • Kita-gun, Kagawa, Japan, 761-0793
      • Kagawa University Hospital ( Site 1108)
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 2360064
      • Yokohama City University Hospital ( Site 1104)
  • Osaka
    • Osakasayama, Osaka, Japan, 5898511
      • Kindai University Hospital ( Site 1107)
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center Hospital and Research Institute ( Site 1105)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03312
    • The Catholic University of Korea Eunpyeong St Mary s Hospital ( Site 1204)
  • Jeonranamdo
    • Hwasun-gun, Jeonranamdo, Korea, Republic of, 58128
      • Chonnam National University Hwasun Hospital ( Site 1202)
  • Kyonggi-do
    • Seongnam-si, Kyonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital ( Site 1205)
    • Suwon-si, Kyonggi-do, Korea, Republic of, 16499
      • Ajou University Hospital ( Site 1200)
  • Seoul
    • Songpa-gu, Seoul, Korea, Republic of, 05505
      • Asan Medical Center ( Site 1201)
  • Taegu-Kwangyokshi
    • Daegu, Taegu-Kwangyokshi, Korea, Republic of, 42601
      • Keimyung University Dongsan Hospital ( Site 1203)
• Mexico
  • Oaxaca, Mexico, 68000
    • Oaxaca Site Management Organization S.C. ( Site 0603)
  • Distrito Federal
    • Cuauhtémoc, Mexico City, Distrito Federal, Mexico, 06100
      • Cryptex Investigación Clínica S.A. de C.V. ( Site 0608)
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 0602)
    • Monterrey, Nuevo Leon, Mexico, 64570
      • Christus Muguerza Clinica Vidriera ( Site 0607)
  • Quintana Roo
    • Cancun, Quintana Roo, Mexico, 77500
      • Centro de Investigacion y Avances Medicos Especializados -CIAME ( Site 0604)
• Peru
  • Lima, Peru, 15033
    • Hospital Nacional Guillermo Almenara Irigoyen ( Site 0700)
  • Lima, Peru, 15072
    • Hospital Nacional Edgardo Rebagliati Martins ( Site 0702)
  • Lima, Peru, 15082
    • Hospital Nacional Arzobispo Loayza ( Site 0703)
  • Lima, Peru, 15102
    • Hospital Nacional Cayetano Heredia ( Site 0704)
  • Muni Metro De Lima
    • Lima, Muni Metro De Lima, Peru, Lima 34
      • Instituto Nacional de Enfermedades Neoplasicas ( Site 0701)
• Poland
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 53-413
      • Dolnoslaskie Centrum Onkologii. ( Site 2507)
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-796
      • Centrum Onkologii im prof Franciszka Lukaszczyka ( Site 2508)
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-826
      • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 2502)
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Glowy i Szyi ( Site
  • Pomorskie
    • Gdynia, Pomorskie, Poland, 81-519
      • Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 2504)
  • Slaskie
    • Gliwice, Slaskie, Poland, 44-101
      • Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 2506)
  • Wielkopolskie
    • Konin, Wielkopolskie, Poland, 62-500
      • Przychodnia Lekarska Komed ( Site 2500)
    • Poznan, Wielkopolskie, Poland, 60-780
      • Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 2509)
• Russian Federation
  • Altayskiy Kray
    • Barnaul, Altayskiy Kray, Russian Federation, 656045
      • Altay Regional Oncology Dispensary ( Site 2611)
  • Moskva
    • Moscow, Moskva, Russian Federation, 115682
      • FSCC FMBA of Russia ( Site 2603)
  • Tatarstan, Respublika
    • Kazan, Tatarstan, Respublika, Russian Federation, 420029
      • Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 2609)
  • Yaroslavskaya Oblast
    • Yaroslavl, Yaroslavskaya Oblast, Russian Federation, 150054
      • Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 2605)
• Spain
  • Barcelona, Spain, 08035
    • H.U. Vall de Hebron ( Site 2700)
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre ( Site 2702)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 2706)
  • Sevilla, Spain, 41014
    • Hospital de Valme ( Site 2705)
  • Zaragoza, Spain, 50009
    • Hospital Clinico Universitario Lozano Blesa ( Site 2703)
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Hospital Duran i Reynals ( Site 2701)
• Taiwan
  • Kaohsiung, Taiwan, 833
    • Chang Gung Medical Foundation. Kaohsiung Branch ( Site 1604)
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital ( Site 1600)
  • Taipei, Taiwan, 10449
    • MacKay Memorial Hospital ( Site 1602)
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital ( Site 1601)
  • Tainan
    • Taiwan, Tainan, Taiwan, 704
      • National Cheng Kung University Hospital ( Site 1603)
• Turkey
  • Ankara, Turkey, 06230
    • Hacettepe Universitesi Tip Fakultesi ( Site 2805)
  • Ankara, Turkey, 06800
    • Ankara Sehir Hastanesi ( Site 2802)
  • Edirne, Turkey, 22030
    • Trakya Universitesi Tip Fakultesi ( Site 2801)
  • Istanbul, Turkey, 34214
    • Medipol Universite Hastanesi ( Site 2800)
  • Izmir, Turkey, 35040
    • Ege Universitesi Tip Fakultesi Hastanesi ( Site 2804)
  • Izmir, Turkey, 35575
    • Medical Park Izmir Hospital ( Site 2807)
  • Malatya, Turkey, 44280
    • Inonu Universitesi Turgut Ozal Tip Merkezi ( Site 2803)
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Christie NHS Foundation Trust ( Site 2903)
  • Aberdeen City
    • Aberdeen, Aberdeen City, United Kingdom, AB25 2ZN
      • Aberdeen Royal Infirmary ( Site 2905)
  • London, City Of
    • London, London, City Of, United Kingdom, SE1 9RT
      • Guy's Hospital in London ( Site 2908)
    • London, London, City Of, United Kingdom, SW3 6JJ
      • Royal Marsden NHS Foundation Trust ( Site 2910)
    • Northwood, London, City Of, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre ( Site 2902)
    • Sutton, London, City Of, United Kingdom, SM2 5PT
      • Royal Marsden Hospital ( Site 2904)
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Nottingham City Hospital ( Site 2907)
  • Somerset
    • Taunton, Somerset, United Kingdom, TA1 5DA
      • Taunton and Somerset Hospital ( Site 2900)
• United States
  • California
    • Fresno, California, United States, 93720
      • California Cancer Associates for Research & Excellence ( Site 0025)
    • San Marcos, California, United States, 92069
      • California Cancer Associates for Research & Excellence ( Site 0059)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center ( Site 0023)
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut Health Center ( Site 0020)
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital-Memorial Cancer Institute ( Site 0069)
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center at Augusta University ( Site 0013)
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers PC ( Site 0028)
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center ( Site 0033)
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville, James Graham Brown Cancer Center ( Site 0045)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute ( Site 0019)
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5936
      • University of Michigan ( Site 0064)
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute ( Site 0054)
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System ( Site 0001)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine ( Site 0060)
  • Montana
    • Billings, Montana, United States, 59102
      • St. Vincent Frontier Cancer Center ( Site 0008)
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0053)
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center ( Site 0002)
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medicine New York Presbyterian Hospital ( Site 0040)
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University ( Site 0051)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina- Chapel Hill ( Site 0056)
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center ( Site 0044)
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center ( Site 0048)
  • Virginia
    • Blacksburg, Virginia, United States, 24060
      • Blue Ridge Cancer Care ( Site 0015)
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute ( Site 0009)
  • Washington
    • Spokane Valley, Washington, United States, 99216
      • Cancer Care Northwest ( Site 0017)
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin- Madison Carbone Cancer Center ( Site 0006)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Has histologically confirmed diagnosis of R/M HNSCC that is considered incurable by local therapies.

Note: Participants with newly-diagnosed HNSCC must be M1/Stage IV.

• Has a primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx.

Note: Primary tumor site of nasopharynx (any histology) or unknown primary tumor (including p16+ unknown primary) are not eligible.

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 agree to use approved contraception during the treatment period for at least 7 days after the last dose of lenvatinib/placebo, or refrain from heterosexual intercourse during this period
• Female participants are not pregnant or breastfeeding, and are not a woman of childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during the treatment period (or 14 days prior to the initiation of study treatment for oral contraception) and for at least 120 days post pembrolizumab, or 30 days post lenvatinib/placebo, whichever occurs last
• Has measurable disease per RECIST 1.1 as assessed by BICR. Note: Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.
• Participants with oropharyngeal cancer must have results from testing of human papillomavirus HPV status.
• Has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.
• Have adequately controlled blood pressure with or without antihypertensive medications.
• Has adequate organ function.

Exclusion Criteria:

• Has a history of any contraindication or has a severe hypersensitivity to any components of pembrolizumab (≥Grade 3) or lenvatinib.
• Has pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
• Has a history of a gastrointestinal condition or procedure that, in the opinion of the investigator, may affect oral study drug absorption.
• Has clinically significant cardiovascular impairment within 12 months of the first dose of study intervention, such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident/transient ischemic attack (TIA)/stroke, cardiac revascularization, or cardiac arrhythmia associated with hemodynamic instability.
• Has disease that is suitable for local therapy administered with curative intent.
• Had PD within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.
• Has had major surgery within 3 weeks before to first dose of study interventions.
• Has difficulty swallowing capsules or ingesting a suspension orally or by a feeding tube.
• Has received prior therapy with lenvatinib or pembrolizumab.
• Received last dose of systemic therapy for locoregionally advanced disease less than 6 months before signing consent.
• 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., CTLA-4, OX-40, CD137).
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
• Has received prior radiotherapy within 2 weeks of start of study intervention.
• Has received a live vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Received an investigational agent or has used an investigational device within 4 weeks prior to study intervention-administration.
• Has a 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 intervention.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.

Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has an active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid) is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy. (e.g., tuberculosis, known viral or bacterial infections, etc.).
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid (RNA) [qualitative] is detected) infection.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention.
• Has had an allogenic tissue/solid organ transplant.
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab with Lenvatinib; Participants receive lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.	Drug: Lenvatinib; Lenvatinib, 20 mg (two 10-mg oral capsules) administered QD; Other Names: E7080; MK-7902; LENVIMA®; Biological: Pembrolizumab; Pembrolizumab (MK-3475), 200 mg, every 3 weeks (Q3W) by intravenous (IV) infusion for up to 35 3-week cycles; Other Names: MK-3475; Keytruda®
Active Comparator: Pembrolizumab with Placebo; Participants receive lenvatinib-matching placebo orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months).	Drug: Placebo; Lenvatinib-matching placebo, oral capsules, administered once daily (QD); Biological: Pembrolizumab; Pembrolizumab (MK-3475), 200 mg, every 3 weeks (Q3W) by intravenous (IV) infusion for up to 35 3-week cycles; Other Names: MK-3475; Keytruda®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR).	ORR is defined as the percentage of participants 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, taking as reference the baseline sum diameters) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experience a CR or PR based on modified RECIST 1.1 will be presented.	Up to approximately 28 months
Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR).	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, 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.	Up to approximately 39 months
Overall Survival (OS)	OS is the time from randomization to death due to any cause.	Up to approximately 39 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death.	Up to approximately 39 months
Number of Participants Who Experienced an Adverse Event (AE)	An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 50 months
Number of Participants Who Discontinued Study Drug Due to an AE	An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 50 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2020
• Primary Completion (Actual): May 30, 2023
• Study Completion (Estimated): December 23, 2024

Study Registration Dates

• First Submitted: December 12, 2019
• First Submitted That Met QC Criteria: December 12, 2019
• First Posted (Actual): December 13, 2019

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: PD-L1; pembrolizumab; lenvatinib; head and neck squamous cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; Pembrolizumab; Lenvatinib
• Other Study ID Numbers: 7902-010; MK-7902-010 (Other Identifier: Protocol number); LEAP-10 (Other Identifier: Merck); 205240 (Registry Identifier: JAPIC-CTI); 2019-003717-34 (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