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)

Squamous Cell Carcinoma of Head and Neck Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04428151
• Other study ID #: 7902-009
• Secondary ID: LEAP-009E7080-G0
• Status: Recruiting
• Phase: Phase 2
• Start date: August 6, 2020
• Est. completion date: February 17, 2027

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to assess the safety and efficacy of lenvatinib in combination with pembrolizumab versus standard of care (SOC) chemotherapy, and to also assess the safety and efficacy of lenvatinib monotherapy in participants with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) that have progressed after platinum therapy and a programmed cell death protein 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) inhibitor. The primary hypothesis is that lenvatinib + pembrolizumab is superior to SOC chemotherapy with respect to ORR per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: February 17, 2027
• Est. primary completion date: July 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically confirmed recurrent (not amenable to curative treatment with local and/or systemic therapies) or metastatic (disseminated) 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 an anti-PD-1/PD-L1 mAb (programmed cell death protein 1/programmed death-ligand 1 monoclonal antibody)

• 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 CT or 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

• 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 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Lenvatinib
20 mg once daily, taken as oral capsules

Biological:
• Pembrolizumab
200 mg 30-minute IV infusion on day 1 of each 21-day cycle

Drug:
• Docetaxel
75 mg/m^2 administered as an IV infusion on day 1 of each 21-day cycle
• Capecitabine
1250 mg/m^2 twice daily on days 1-14 of each 21-day cycle, taken as oral tablets
• Paclitaxel
80 mg/m^2 administered as an IV infusion on days 1, 8, and 15 of each 21-day cycle
• 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
• Lenvatinib
24 mg once daily, taken as oral capsules

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital ( Site 0110)	Adelaide	South Australia
Australia	Monash Health ( Site 0102)	Clayton	Victoria
Australia	The Townsville Hospital ( Site 0107)	Douglas	Queensland
Australia	Gallipoli Medical Research Ltd-GMRF CTU ( Site 0105)	Greenslopes	Queensland
Australia	Mid North Coast Cancer Institute ( Site 0109)	Port Macquarie	New South Wales
Australia	Blacktown Hospital ( Site 0101)	Sydney	New South Wales
Brazil	Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 0806)	Porto Alegre	Rio Grande Do Sul
Brazil	A. C. Camargo Cancer Center ( Site 0809)	Sao Paulo
Canada	Tom Baker Cancer Centre ( Site 0304)	Calgary	Alberta
Canada	Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0307)	Hamilton	Ontario
Canada	Sunnybrook Research Institute ( Site 0308)	Toronto	Ontario
Canada	BC Cancer-Vancouver Center ( Site 0306)	Vancouver	British Columbia
Colombia	Administradora Country S.A.S - Clínica del Country ( Site 0407)	Bogotá	Cundinamarca
Colombia	Instituto de Cancerología ( Site 0408)	Medellin	Antioquia
Colombia	Oncomédica S.A.S ( Site 0409)	Montería	Cordoba
Colombia	Sociedad De Oncologia Y Hematologia Del Cesar ( Site 0404)	Valledupar	Cesar
Denmark	Rigshospitalet University Hospital Copenhagen ( Site 1000)	Copenhagen	Hovedstaden
France	Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne-ONCOLOGY ( Site 0510)	Clermont-Ferrand	Puy-de-Dome
France	Hopital La Timone ( Site 0503)	Marseille	Bouches-du-Rhone
France	Centre de Cancerologie du Grand Montpellier ( Site 0508)	Montpellier	Herault
France	Institut Curie ( Site 0500)	Paris
France	Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen ( Site 0509)	Rouen	Seine-Maritime
France	Institut Gustave Roussy ( Site 0505)	Villejuif	Val-de-Marne
Israel	Soroka Medical Center-Oncology ( Site 0604)	Be'er Sheva
Israel	Rambam Health Care Campus-Oncology Division ( Site 0602)	Haifa
Israel	Hadassah Medical Center. Ein Kerem ( Site 0601)	Jerusalem
Israel	Chaim Sheba Medical Center ( Site 0600)	Ramat Gan
Korea, Republic of	Seoul National University Bundang Hospital ( Site 1801)	Seongnam	Kyonggi-do
Korea, Republic of	Samsung Medical Center ( Site 1803)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 1800)	Seoul
Korea, Republic of	Ajou University Hospital ( Site 1802)	Suwon	Kyonggi-do
Norway	Oslo universitetssykehus, Radiumhospitalet ( Site 1102)	Oslo
Portugal	Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 1400)	Porto
Portugal	Centro Hospitalar Vila Nova de Gaia. Espinho EPE ( Site 1401)	Vila Nova de Gaia	Porto
Romania	Spitalul Clinic Col?ea ( Site 1708)	Bucure?ti	Bucuresti
Romania	S.C.Focus Lab Plus S.R.L ( Site 1703)	Bucuresti
Romania	Cardiomed SRL Cluj-Napoca ( Site 1701)	Cluj Napoca	Cluj
Romania	Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1702)	Cluj Napoca	Cluj
Romania	S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1704)	Craiova	Dolj
Romania	S.C. Radiotherapy Center Cluj S.R.L ( Site 1706)	Floresti	Cluj
Romania	Cabinet Medical Oncomed ( Site 1707)	Timi?oara	Timis
Spain	Centro Oncologico de Galicia ( Site 0706)	A Coruna	Galicia
Spain	HOSPITAL CLÍNIC DE BARCELONA ( Site 0707)	Barcelona	Cataluna
Spain	Hospital Universitari Vall d Hebron ( Site 0701)	Barcelona
Spain	Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 0700)	Hospitalet de Llobregat	Barcelona
Spain	Hospital Ramon y Cajal ( Site 0705)	Madrid
Spain	Hospital Virgen de la Victoria ( Site 0702)	Malaga
Spain	Hospital General de Valencia ( Site 0703)	Valencia	Valenciana, Comunitat
Taiwan	Chang Gung Medical Foundation - Kaohsiung ( Site 1204)	Kaohsiung
Taiwan	China Medical University Hospital ( Site 1205)	Taichung
Taiwan	Taichung Veterans General Hospital ( Site 1206)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 1202)	Tainan
Taiwan	National Taiwan University Hospital ( Site 1200)	Taipei
Taiwan	Taipei Veterans General Hospital ( Site 1201)	Taipei
Taiwan	Chang Gung Memorial Hospital - Linkou Branch ( Site 1203)	Taoyuan County	Taoyuan
United Kingdom	Aberdeen Royal Infirmary ( Site 0911)	Aberdeen	Aberdeen City
United Kingdom	Castle Hill Hospital ( Site 0910)	Cottingham	East Riding Of Yorkshire
United Kingdom	The Beatson West of Scotland Cancer Centre ( Site 0909)	Glasgow	Glasgow City
United Kingdom	Charing Cross Hospital ( Site 0908)	London	London, City Of
United Kingdom	Guy s and St Thomas Hospital NHS Foundation Trust ( Site 0903)	London	Great Britain
United Kingdom	Royal Marsden Hospital ( Site 0902)	London	London, City Of
United Kingdom	The Christie NHS Foundation Trust ( Site 0907)	Manchester
United Kingdom	University Hospital Southampton NHS Foundation Trust ( Site 0905)	Southampton	Hampshire
United Kingdom	Royal Marsden Hospital. ( Site 0901)	Sutton	Surrey
United Kingdom	Musgrove Park Hospital ( Site 0904)	Taunton	Somerset
United States	VA Ann Arbor Healthcare System ( Site 1584)	Ann Arbor	Michigan
United States	Georgia Cancer Center at Augusta University ( Site 1575)	Augusta	Georgia
United States	University of Maryland Greenebaum Cancer Center ( Site 1522)	Baltimore	Maryland
United States	Mary Bird Perkins Cancer Center Baton Rouge ( Site 1622)	Baton Rouge	Louisiana
United States	Our Lady of the Lake RMC-Clinical Research ( Site 1624)	Baton Rouge	Louisiana
United States	St. Vincent Frontier Cancer Center ( Site 1507)	Billings	Montana
United States	Boston Medical Center ( Site 1605)	Boston	Massachusetts
United States	Medical University of South Carolina ( Site 1579)	Charleston	South Carolina
United States	Levine Cancer Institute ( Site 1590)	Charlotte	North Carolina
United States	Rush University Medical Center ( Site 1560)	Chicago	Illinois
United States	University of Cincinnati Medical Center ( Site 1567)	Cincinnati	Ohio
United States	Cleveland Clinic Main ( Site 1598)	Cleveland	Ohio
United States	University Hospital Cleveland ( Site 1578)	Cleveland	Ohio
United States	The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C	Columbus	Ohio
United States	Barbara Ann Karmanos Cancer Institute ( Site 1566)	Detroit	Michigan
United States	Henry Ford Health System ( Site 1544)	Detroit	Michigan
United States	City of Hope ( Site 1519)	Duarte	California
United States	Duke Cancer Institute ( Site 1541)	Durham	North Carolina
United States	NorthShore University HealthSystem - Evanston Hospital ( Site 1614)	Evanston	Illinois
United States	Inova Schar Cancer Institute ( Site 1550)	Fairfax	Virginia
United States	The Center For Cancer And Blood Disorders ( Site 1569)	Fort Worth	Texas
United States	Hematology Oncology Associates of Fredericksburg ( Site 1537)	Fredericksburg	Virginia
United States	UF Health ( Site 1554)	Gainesville	Florida
United States	Gettysburg Cancer Center ( Site 1594)	Gettysburg	Pennsylvania
United States	St Francis Cancer Center-Research Office ( Site 1607)	Greenville	South Carolina
United States	John Theurer Cancer Center at Hackensack University Medical Center ( Site 1555)	Hackensack	New Jersey
United States	Hattiesburg Clinic ( Site 1515)	Hattiesburg	Mississippi
United States	Penn State Hershey Medical Center ( Site 1561)	Hershey	Pennsylvania
United States	University of Iowa ( Site 1572)	Iowa City	Iowa
United States	Jackson Oncology Associates, PLLC-Clinical Trials ( Site 1625)	Jackson	Mississippi
United States	UCLA Hematology/Oncology - Westwood (Building 100) ( Site 1568)	Los Angeles	California
United States	Norton Hospital-Norton Cancer Institute - Downtown ( Site 1601)	Louisville	Kentucky
United States	Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 1521)	Marietta	Georgia
United States	Medical College of Wisconsin Clinical Cancer Center ( Site 1574)	Milwaukee	Wisconsin
United States	Perlmutter Cancer Center at Winthrop Oncology Hematology Associates NYU Langone Health ( Site 1597)	Mineola	New York
United States	IU Health Ball Memorial Hospital, Inc.-IU Health Ball Memorial Cancer Center ( Site 1612)	Muncie	Indiana
United States	Rutgers Cancer Institute of New Jersey ( Site 1523)	New Brunswick	New Jersey
United States	Yale-New Haven Hospital-Yale Cancer Center ( Site 1505)	New Haven	Connecticut
United States	Laura and Isaac Perlmutter Cancer Center ( Site 1582)	New York	New York
United States	Oncology Hematology West P.C. dba Nebraska Cancer Specialists ( Site 1627)	Omaha	Nebraska
United States	University Of Nebraska Medical Center ( Site 1570)	Omaha	Nebraska
United States	Mid Florida Hematology and Oncology Center ( Site 1606)	Orange City	Florida
United States	Mercy Health-Paducah Medical Oncology and Hematology ( Site 1623)	Paducah	Kentucky
United States	Fox Chase Cancer Center ( Site 1502)	Philadelphia	Pennsylvania
United States	Beacon Cancer Care ( Site 1599)	Post Falls	Idaho
United States	Washington University School of Medicine ( Site 1500)	Saint Louis	Missouri
United States	Huntsman Cancer Institute ( Site 1532)	Salt Lake City	Utah
United States	Utah Cancer Specialists ( Site 1621)	Salt Lake City	Utah
United States	Memorial Health University Medical Center ( Site 1626)	Savannah	Georgia
United States	MultiCare Health System-MultiCare Oncology - Puget Sound ( Site 1609)	Tacoma	Washington
United States	Oklahoma Cancer Specialists and Research Institute, LLC ( Site 1508)	Tulsa	Oklahoma
United States	Georgetown University Medical Center ( Site 1520)	Washington	District of Columbia
United States	Cleveland Clinic Florida ( Site 1596)	Weston	Florida
United States	University of Kansas Cancer Center ( Site 1538)	Westwood	Kansas
United States	University of Massachusetts Chan Medical School ( Site 1616)	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Eisai Inc.

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Colombia,  Denmark,  France,  Israel,  Korea, Republic of,  Norway,  Portugal,  Romania,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants who have 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 occurs first. Responses are according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR).	Up to approximately 4 years
Secondary	Progression-Free Survival (PFS)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Responses are according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR).	Up to approximately 4 years
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 4 years
Secondary	Duration of Response (DOR)	DOR is 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 occurs first. Responses are according to modified RECIST 1.1 as assessed by BICR.	Up to approximately 4 years
Secondary	Number of Participants Who Experienced One or More Adverse Events (AEs)	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.	Up to approximately 4 years
Secondary	Number of Participants Who Discontinued Study Intervention Due to 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 discontinue study treatment due to an AE will be presented.	Up to approximately 4 years

External Links

•   Merck Clinical Trials Information