Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) vs. Standard Chemotherapy and Lenvatinib Monotherapy in Participants With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma That Progressed After Platinum Therapy and Immunotherapy (MK-7902-009/E7080-G000-228/LEAP-009)

A Phase 2, Randomized, Open-label Three-arm Clinical Study to Evaluate the Safety and Efficacy of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care Chemotherapy and Lenvatinib Monotherapy in Participants With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) That Have Progressed After Platinum Therapy and Immunotherapy (PD-1/PD-L1 Inhibitors) (LEAP-009)

Researchers are looking for new ways to treat people with head and neck cancer whose cancer has come back after treatment (recurrent) or whose cancer has spread to other parts of the body (metastatic). Some people with recurrent or metastatic head and neck cancer are treated with chemotherapy and immunotherapy, but the cancer gets worse.

The goal of this study is to learn if more people who receive lenvatinib and pembrolizumab have a better overall survival rate than people who receive standard chemotherapy treatment.

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma of Head and Neck
• Intervention / Treatment: Drug: Lenvatinib; Biological: Pembrolizumab; Drug: Lenvatinib; Drug: Docetaxel; Drug: Capecitabine; Drug: Paclitaxel; Drug: Cetuximab

Detailed Description

With Amendment 7, participants will discontinue lenvatinib and pembrolizumab and lenvatinib monotherapy, unless discussed with the Sponsor.

A protocol-specified periodic safety review was completed with a data cut-off of 31-May-2024 (Primary Completion Date) and served as the final analysis of the primary outcome measure. Per protocol, 34 participants enrolled after the primary completion date and will be analyzed in the End of Trial analysis.

• Study Type: Interventional
• Enrollment (Actual): 408
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Port Macquarie, New South Wales, Australia, 2444
      • Mid North Coast Cancer Institute ( Site 0109)
    • Sydney, New South Wales, Australia, 2148
      • Blacktown Hospital ( Site 0101)
  • Queensland
    • Douglas, Queensland, Australia, 4814
      • The Townsville Hospital ( Site 0107)
    • Greenslopes, Queensland, Australia, 4120
      • Gallipoli Medical Research Ltd-GMRF CTU ( Site 0105)
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital ( Site 0110)
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health ( Site 0102)
• Brazil
  • São Paulo, Brazil, 01509-010
    • A. C. Camargo Cancer Center ( Site 0809)
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 0806)
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Arthur J.E. Child Comprehensive Cancer Centre ( Site 0304)
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer-Vancouver Center ( Site 0306)
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0307)
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute ( Site 0308)
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 50034
      • Instituto de Cancerología ( Site 0408)
  • Cesar Department
    • Valledupar, Cesar Department, Colombia, 200001
      • Sociedad De Oncologia Y Hematologia Del Cesar ( Site 0404)
  • Cundinamarca
    • Bogotá, Cundinamarca, Colombia, 110221
      • Administradora Country S.A.S - Clínica del Country ( Site 0407)
  • Departamento de Córdoba
    • Montería, Departamento de Córdoba, Colombia, 230002
      • IMAT S.A.S ( Site 0409)
• Denmark
  • Capital Region
    • Copenhagen, Capital Region, Denmark, 2100
      • Rigshospitalet University Hospital Copenhagen ( Site 1000)
• France
  • Paris, France, 75005
    • Institut Curie ( Site 0500)
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13385
      • Hopital La Timone ( Site 0503)
  • Herault
    • Montpellier, Herault, France, 34070
      • Centre de Cancerologie du Grand Montpellier ( Site 0508)
  • Puy-de-Dome
    • Clermont-Ferrand, Puy-de-Dome, France, 63003
      • Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne-ONCOLOGY ( Site 0510)
  • Seine-Maritime
    • Rouen, Seine-Maritime, France, 76038
      • Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen ( Site 0509)
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94800
      • Institut Gustave Roussy ( Site 0505)
• Israel
  • Beersheba, Israel, 8400000
    • Soroka Medical Center-Oncology ( Site 0604)
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus-Oncology Division ( Site 0602)
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center. Ein Kerem ( Site 0601)
  • Ramat Gan, Israel, 5265601
    • Chaim Sheba Medical Center ( Site 0600)
• Norway
  • Oslo, Norway, 0379
    • Oslo universitetssykehus, Radiumhospitalet ( Site 1102)
• Portugal
  • Porto, Portugal, 4200-072
    • Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 1400)
  • Porto District
    • Vila Nova de Gaia, Porto District, Portugal, 4434-502
      • Unidade Local de Saude Gaia/Espinho - Hospital Eduardo Santos Silva ( Site 1401)
• Romania
  • București
    • Bucharest, București, Romania, 013823
      • MEMORIAL HEALTHCARE INTERNATIONAL S.R.L. ( Site 1703)
    • Bucharest, București, Romania, 030171
      • Spitalul Clinic Colțea ( Site 1708)
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400015
      • Cardiomed SRL Cluj-Napoca ( Site 1701)
    • Cluj-Napoca, Cluj, Romania, 400015
      • Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1702)
    • Floreşti, Cluj, Romania, 407280
      • S.C. Radiotherapy Center Cluj S.R.L ( Site 1706)
  • Dolj
    • Craiova, Dolj, Romania, 200542
      • S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1704)
  • Timiș County
    • Timișoara, Timiș County, Romania, 300239
      • Cabinet Medical Oncomed ( Site 1707)
• South Korea
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System ( Site 1800)
  • Seoul, South Korea, 06351
    • Samsung Medical Center ( Site 1803)
  • Kyonggi-do
    • Seongnam, Kyonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital ( Site 1801)
    • Suwon, Kyonggi-do, South Korea, 16499
      • Ajou University Hospital ( Site 1802)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d Hebron ( Site 0701)
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal ( Site 0705)
  • Málaga, Spain, 29010
    • Hospital Virgen de la Victoria ( Site 0702)
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 0700)
  • Catalonia
    • Barcelona, Catalonia, Spain, 08036
      • HOSPITAL CLÍNIC DE BARCELONA ( Site 0707)
  • Galicia
    • A Coruña, Galicia, Spain, 15009
      • Centro Oncologico de Galicia ( Site 0706)
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46014
      • Hospital General de Valencia ( Site 0703)
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Chang Gung Medical Foundation - Kaohsiung ( Site 1204)
  • Taichung, Taiwan, 404332
    • China Medical University Hospital ( Site 1205)
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital ( Site 1206)
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital ( Site 1202)
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital ( Site 1200)
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital ( Site 1201)
  • Taoyuan District, Taiwan, 333
    • Chang Gung Memorial Hospital - Linkou Branch ( Site 1203)
• United Kingdom
  • Manchester, United Kingdom, m20 4bx
    • The Christie NHS Foundation Trust ( Site 0907)
  • Aberdeen City
    • Aberdeen, Aberdeen City, United Kingdom, AB25 2ZN
      • Aberdeen Royal Infirmary ( Site 0911)
  • East Riding Of Yorkshire
    • Cottingham, East Riding Of Yorkshire, United Kingdom, HU16 5JQ
      • Castle Hill Hospital ( Site 0910)
  • Glasgow City
    • Glasgow, Glasgow City, United Kingdom, G12 0YN
      • The Beatson West of Scotland Cancer Centre ( Site 0909)
  • Great Britain
    • London, Great Britain, United Kingdom, SE1 9RT
      • Guy s and St Thomas Hospital NHS Foundation Trust ( Site 0903)
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • University Hospital Southampton NHS Foundation Trust ( Site 0905)
  • London, City of
    • London, London, City of, United Kingdom, SW3 6JJ
      • Royal Marsden Hospital ( Site 0902)
    • London, London, City of, United Kingdom, W6 8RF
      • Charing Cross Hospital ( Site 0908)
  • Somerset
    • Taunton, Somerset, United Kingdom, TA1 5DA
      • Musgrove Park Hospital ( Site 0904)
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Royal Marsden Hospital. ( Site 0901)
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope ( Site 1519)
    • Los Angeles, California, United States, 90095
      • UCLA Hematology/Oncology - Westwood (Building 100) ( Site 1568)
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale-New Haven Hospital-Yale Cancer Center ( Site 1505)
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University Medical Center ( Site 1520)
  • Florida
    • Gainesville, Florida, United States, 32608
      • UF Health ( Site 1554)
    • Orange City, Florida, United States, 32763
      • Mid Florida Hematology and Oncology Center ( Site 1606)
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida ( Site 1596)
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center at Augusta University ( Site 1575)
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 1521)
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center ( Site 1626)
  • Idaho
    • Post Falls, Idaho, United States, 83854
      • Beacon Cancer Care ( Site 1599)
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Rush University Medical Center ( Site 1560)
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem - Evanston Hospital ( Site 1614)
  • Indiana
    • Muncie, Indiana, United States, 47303
      • IU Health Ball Memorial Hospital, Inc.-IU Health Ball Memorial Cancer Center ( Site 1612)
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa ( Site 1572)
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center ( Site 1538)
  • Kentucky
    • Louisville, Kentucky, United States, 40205
      • Norton Hospital-Norton Cancer Institute - Downtown ( Site 1601)
    • Paducah, Kentucky, United States, 42003
      • Mercy Health-Paducah Cancer Center ( Site 1623)
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Our Lady of the Lake RMC-Clinical Research ( Site 1624)
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center Baton Rouge ( Site 1622)
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Cancer Center ( Site 1522)
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center ( Site 1605)
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Chan Medical School ( Site 1616)
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • VA Ann Arbor Healthcare System ( Site 1584)
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute ( Site 1566)
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System ( Site 1544)
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic ( Site 1515)
    • Jackson, Mississippi, United States, 39202
      • Jackson Oncology Associates, PLLC-Clinical Trials ( Site 1625)
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine ( Site 1500)
  • Montana
    • Billings, Montana, United States, 59102
      • St. Vincent Frontier Cancer Center ( Site 1507)
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • University Of Nebraska Medical Center ( Site 1570)
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West P.C. dba Nebraska Cancer Specialists ( Site 1627)
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center ( Site 1555)
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey ( Site 1523)
  • New York
    • Mineola, New York, United States, 11501
      • Perlmutter Cancer Center at Winthrop Oncology Hematology Associates NYU Langone Health ( Site 1597)
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center ( Site 1582)
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute ( Site 1590)
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute ( Site 1541)
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center ( Site 1567)
    • Cleveland, Ohio, United States, 44106
      • University Hospital Cleveland ( Site 1578)
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main ( Site 1598)
    • Columbus, Ohio, United States, 43210
      • The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C ( Site 1558)
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute, LLC ( Site 1508)
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Gettysburg Cancer Center ( Site 1594)
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center ( Site 1561)
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center ( Site 1502)
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina ( Site 1579)
    • Greenville, South Carolina, United States, 29607
      • St Francis Cancer Center-Research Office ( Site 1607)
  • Texas
    • Fort Worth, Texas, United States, 76104
      • The Center For Cancer And Blood Disorders ( Site 1569)
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists ( Site 1621)
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute ( Site 1532)
  • Virginia
    • Fairfax, Virginia, United States, 22031-4867
      • Inova Schar Cancer Institute ( Site 1550)
    • Fredericksburg, Virginia, United States, 22408
      • Hematology Oncology Associates of Fredericksburg ( Site 1537)
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System-MultiCare Oncology - Puget Sound ( Site 1609)
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Clinical Cancer Center ( Site 1574)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologically confirmed recurrent (not amenable to curative treatment with local and/or systemic therapies) or metastatic (disseminated) head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies
• Disease progression at any time during or after treatment with a platinum-containing (e.g., carboplatin or cisplatin) regimen
• Disease progression on or after treatment with a programmed cell death protein 1/programmed death-ligand 1 monoclonal antibody (anti-PD-1/PD-L1 mAb)
• Pre-study imaging that demonstrates evidence of disease progression based on investigator review of at least 2 pre-study images per RECIST 1.1, following initiation of treatment with a PD-1/PD-L1 inhibitor
• Measurable disease by computed tomography scan (CT) or magnetic resonance imaging (MRI) based on Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as verified by blinded independent central review (BICR). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of the first dose of study intervention

• Male participants are eligible to participate if they agree to the following during the intervention period and for at least 1 week after the last dose of lenvatinib, 3 months after the last dose of capecitabine and paclitaxel, and 6 months after the last dose of docetaxel:

  • Refrain from donating sperm
  • Be abstinent 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 azoospermic
  • Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

• A 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 woman of childbearing potential (WOCBP)
  • 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 or 1 month post lenvatinib, whichever occurs last (Arms 1 and 3), or during the intervention period and for at least 6 months after the last dose of capecitabine, docetaxel, paclitaxel; and 2 months after the last dose of cetuximab (Arm 2)
  • Female participants who randomize to Arm 2 must also agree not to donate or freeze/store eggs during the intervention period and for at least 6 months after the last dose of capecitabine, docetaxel, paclitaxel; and 2 months after the last dose of cetuximab
• Adequately controlled blood pressure (BP) with or without antihypertensive medications
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
• Adequate organ function

Exclusion Criteria:

• Disease that is suitable for local therapy administered with curative intent
• Life expectancy of less than 3 months and/or has rapidly progressing disease in the opinion of the treating investigator
• History of (noninfectious) pneumonitis/interstitial lung disease that required steroids, or has current pneumonitis/interstitial lung disease
• Active infection requiring systemic therapy
• 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 to the first dose of study drug
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Known additional malignancy that is progressing or has required active systemic treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ that have undergone potentially curative therapy
• Active autoimmune disease that has required systemic treatment in the past 2 years
• Had an allogeneic tissue/solid organ transplant
• Known history of human immunodeficiency virus (HIV) infection
• History of any contraindication or has a severe hypersensitivity to any components of pembrolizumab, lenvatinib or SOC chemotherapy.
• Pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
• History of a gastrointestinal malabsorption or any other condition or procedure that may affect oral study drug absorption
• Had major surgery within 3 weeks prior to first dose of study interventions
• Clinically significant cardiovascular impairment within 12 months of the first dose of study drug
• Active tuberculosis
• Has difficulty swallowing capsules or ingesting a suspension orally, or by a feeding tube
• Prior treatment with lenvatinib
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Study Day 1 or has not recovered from adverse events (AEs) due to a previously administered agent. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible
• Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: Administration of killed vaccines is allowed
• Previously treated with 4 or more systemic regimens given for recurrent/metastatic disease
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• 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: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenvatinib + Pembrolizumab; Participants will be treated with the combination of lenvatinib (once daily 20 mg oral dose) plus pembrolizumab (200 mg 30-minute intravenous (IV) infusion on Day 1 of each 21-day cycle for 35 cycles), until centrally verified disease progression, or until a protocol-specified discontinuation criterion is met. Participants may receive up to an additional 17 cycles of pembrolizumab as Second Course treatment, with or without lenvatinib.	Drug: Lenvatinib; 20 mg once daily, taken as oral capsules; Other Names: E7080; MK-7902; LENVIMA®; Biological: Pembrolizumab; 200 mg 30-minute IV infusion on day 1 of each 21-day cycle; Other Names: MK-3475; SCH 900475; KEYTRUDA®; Drug: Lenvatinib; 24 mg once daily, taken as oral capsules; Other Names: E7080; MK-7902; LENVIMA®
Active Comparator: SOC Chemotherapy; Participants will be treated with investigator's choice of standard of care (SOC) chemotherapy (docetaxel, paclitaxel, cetuximab, or capecitabine) until centrally verified disease progression, or until a protocol-specified discontinuation criterion is met.	Drug: Docetaxel; 75 mg/m^2 administered as an IV infusion on day 1 of each 21-day cycle; Other Names: TAXOTERE®; Drug: Capecitabine; 1250 mg/m^2 twice daily on days 1-14 of each 21-day cycle, taken as oral tablets; Other Names: Xeloda®; Drug: Paclitaxel; 80 mg/m^2 administered as an IV infusion on days 1, 8, and 15 of each 21-day cycle; Other Names: Taxol; Drug: Cetuximab; 400 mg/m^2 loading dose, followed by 250 mg/m^2 administered as an IV infusion on days 1, 8, and 15 of each 21-day cycle; Other Names: ERBITUX®
Active Comparator: Lenvatinib Monotherapy; Participants will be treated with lenvatinib monotherapy (once daily 24 mg oral dose) until centrally verified disease progression, or until a protocol-specified discontinuation criterion is met.	Drug: Lenvatinib; 20 mg once daily, taken as oral capsules; Other Names: E7080; MK-7902; LENVIMA®; Drug: Lenvatinib; 24 mg once daily, taken as oral capsules; Other Names: E7080; MK-7902; LENVIMA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause.	Up to approximately 45 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Responses were according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR). RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. 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 have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD.	Up to approximately 45 months
Objective Response Rate (ORR)	ORR was defined as the percentage of participants who had a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of the diameters of target lesions) until progressive disease (PD) or death due to any cause, whichever occurred first. Responses were according to modified RECIST 1.1 as assessed by BICR. RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.	Up to approximately 45 months
Duration of Response (DOR)	DOR was defined as the time from the first documented evidence of complete response (CR: disappearance of all target lesions) or partial response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of the diameters of target lesions) until progressive disease (PD) or death due to any cause, whichever occurred first. Responses were according to modified RECIST 1.1 as assessed by BICR.	Up to approximately 45 months
Number of Participants Who Experienced One or More Adverse Events (AEs)	An AE was 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 was presented.	Up to approximately 5 years
Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)	An AE was 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 discontinue study treatment due to an AE was presented.	Up to approximately 5 years

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 Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2020
• Primary Completion (Actual): May 31, 2024
• Study Completion (Actual): October 30, 2025

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: June 9, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Parkinson Disease 4, Autosomal Dominant Lewy Body; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Docetaxel; Capecitabine; Cetuximab; Paclitaxel; pembrolizumab; lenvatinib
• Other Study ID Numbers: 7902-009; LEAP-009 (Other Identifier: MSD); E7080-G000-228 (Other Identifier: Eisai); MK-7902-009 (Other Identifier: MSD); 2019-000569-19 (EudraCT Number); U1111-1278-2707 (Registry Identifier: UTN); 2022-500820-31-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/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