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)
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Interventions
- Registration Number
- NCT04428151
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 408
-
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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lenvatinib + Pembrolizumab 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. Lenvatinib + Pembrolizumab Lenvatinib 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. SOC Chemotherapy Docetaxel 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. SOC Chemotherapy Capecitabine 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. SOC Chemotherapy Paclitaxel 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. SOC Chemotherapy Cetuximab 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. Lenvatinib Monotherapy Lenvatinib 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Up to approximately 45 months OS was defined as the time from randomization to death due to any cause.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Up to approximately 45 months 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.
Objective Response Rate (ORR) Up to approximately 45 months 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.
Duration of Response (DOR) Up to approximately 45 months 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.
Number of Participants Who Experienced One or More Adverse Events (AEs) Up to approximately 5 years 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.
Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE) Up to approximately 5 years 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.
Trial Locations
- Locations (120)
Rush University Medical Center ( Site 1560)
🇺🇸Chicago, Illinois, United States
Cleveland Clinic Main ( Site 1598)
🇺🇸Cleveland, Ohio, United States
Boston Medical Center ( Site 1605)
🇺🇸Boston, Massachusetts, United States
Chang Gung Memorial Hospital - Linkou Branch ( Site 1203)
🇨🇳Taoyuan County, Taoyuan, Taiwan
Barbara Ann Karmanos Cancer Institute ( Site 1566)
🇺🇸Detroit, Michigan, United States
Henry Ford Health System ( Site 1544)
🇺🇸Detroit, Michigan, United States
Duke Cancer Institute ( Site 1541)
🇺🇸Durham, North Carolina, United States
Utah Cancer Specialists ( Site 1621)
🇺🇸Salt Lake City, Utah, United States
Royal Adelaide Hospital ( Site 0110)
🇦🇺Adelaide, South Australia, Australia
Oklahoma Cancer Specialists and Research Institute, LLC ( Site 1508)
🇺🇸Tulsa, Oklahoma, United States
Mid North Coast Cancer Institute ( Site 0109)
🇦🇺Port Macquarie, New South Wales, Australia
Gallipoli Medical Research Ltd-GMRF CTU ( Site 0105)
🇦🇺Greenslopes, Queensland, Australia
University of Kansas Cancer Center ( Site 1538)
🇺🇸Westwood, Kansas, United States
Perlmutter Cancer Center at Winthrop Oncology Hematology Associates NYU Langone Health ( Site 1597)
🇺🇸Mineola, New York, United States
Hattiesburg Clinic ( Site 1515)
🇺🇸Hattiesburg, Mississippi, United States
Rutgers Cancer Institute of New Jersey ( Site 1523)
🇺🇸New Brunswick, New Jersey, United States
Fox Chase Cancer Center ( Site 1502)
🇺🇸Philadelphia, Pennsylvania, United States
UCLA Hematology/Oncology - Westwood (Building 100) ( Site 1568)
🇺🇸Los Angeles, California, United States
Mary Bird Perkins Cancer Center Baton Rouge ( Site 1622)
🇺🇸Baton Rouge, Louisiana, United States
Washington University School of Medicine ( Site 1500)
🇺🇸Saint Louis, Missouri, United States
University of Maryland Greenebaum Cancer Center ( Site 1522)
🇺🇸Baltimore, Maryland, United States
John Theurer Cancer Center at Hackensack University Medical Center ( Site 1555)
🇺🇸Hackensack, New Jersey, United States
MultiCare Health System-MultiCare Oncology - Puget Sound ( Site 1609)
🇺🇸Tacoma, Washington, United States
Gettysburg Cancer Center ( Site 1594)
🇺🇸Gettysburg, Pennsylvania, United States
The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C
🇺🇸Columbus, Ohio, United States
Inova Schar Cancer Institute ( Site 1550)
🇺🇸Fairfax, Virginia, United States
Hematology Oncology Associates of Fredericksburg ( Site 1537)
🇺🇸Fredericksburg, Virginia, United States
Huntsman Cancer Institute ( Site 1532)
🇺🇸Salt Lake City, Utah, United States
Blacktown Hospital ( Site 0101)
🇦🇺Sydney, New South Wales, Australia
Tom Baker Cancer Centre ( Site 0304)
🇨🇦Calgary, Alberta, Canada
Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 0806)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
BC Cancer-Vancouver Center ( Site 0306)
🇨🇦Vancouver, British Columbia, Canada
Hopital La Timone ( Site 0503)
🇫🇷Marseille, Bouches-du-Rhone, France
Oslo universitetssykehus, Radiumhospitalet ( Site 1102)
🇳🇴Oslo, Norway
Samsung Medical Center ( Site 1803)
🇰🇷Seoul, Korea, Republic of
Centre de Cancerologie du Grand Montpellier ( Site 0508)
🇫🇷Montpellier, Herault, France
Soroka Medical Center-Oncology ( Site 0604)
🇮🇱Be'er Sheva, Israel
Chaim Sheba Medical Center ( Site 0600)
🇮🇱Ramat Gan, Israel
Rambam Health Care Campus-Oncology Division ( Site 0602)
🇮🇱Haifa, Israel
Hadassah Medical Center. Ein Kerem ( Site 0601)
🇮🇱Jerusalem, Israel
Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 0700)
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Hospital Virgen de la Victoria ( Site 0702)
🇪🇸Malaga, Spain
HOSPITAL CLÍNIC DE BARCELONA ( Site 0707)
🇪🇸Barcelona, Cataluna, Spain
Musgrove Park Hospital ( Site 0904)
🇬🇧Taunton, Somerset, United Kingdom
The Christie NHS Foundation Trust ( Site 0907)
🇬🇧Manchester, United Kingdom
Aberdeen Royal Infirmary ( Site 0911)
🇬🇧Aberdeen, Aberdeen City, United Kingdom
Hospital Universitari Vall d Hebron ( Site 0701)
🇪🇸Barcelona, Spain
Hospital Ramon y Cajal ( Site 0705)
🇪🇸Madrid, Spain
Charing Cross Hospital ( Site 0908)
🇬🇧London, London, City Of, United Kingdom
University Hospital Southampton NHS Foundation Trust ( Site 0905)
🇬🇧Southampton, Hampshire, United Kingdom
Royal Marsden Hospital ( Site 0902)
🇬🇧London, London, City Of, United Kingdom
The Beatson West of Scotland Cancer Centre ( Site 0909)
🇬🇧Glasgow, Glasgow City, United Kingdom
Guy s and St Thomas Hospital NHS Foundation Trust ( Site 0903)
🇬🇧London, Great Britain, United Kingdom
Sunnybrook Research Institute ( Site 0308)
🇨🇦Toronto, Ontario, Canada
University Of Nebraska Medical Center ( Site 1570)
🇺🇸Omaha, Nebraska, United States
Oncology Hematology West P.C. dba Nebraska Cancer Specialists ( Site 1627)
🇺🇸Omaha, Nebraska, United States
Medical College of Wisconsin Clinical Cancer Center ( Site 1574)
🇺🇸Milwaukee, Wisconsin, United States
City of Hope ( Site 1519)
🇺🇸Duarte, California, United States
Georgetown University Medical Center ( Site 1520)
🇺🇸Washington, District of Columbia, United States
Mid Florida Hematology and Oncology Center ( Site 1606)
🇺🇸Orange City, Florida, United States
Beacon Cancer Care ( Site 1599)
🇺🇸Post Falls, Idaho, United States
Cleveland Clinic Florida ( Site 1596)
🇺🇸Weston, Florida, United States
Georgia Cancer Center at Augusta University ( Site 1575)
🇺🇸Augusta, Georgia, United States
Memorial Health University Medical Center ( Site 1626)
🇺🇸Savannah, Georgia, United States
Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 1521)
🇺🇸Marietta, Georgia, United States
IU Health Ball Memorial Hospital, Inc.-IU Health Ball Memorial Cancer Center ( Site 1612)
🇺🇸Muncie, Indiana, United States
NorthShore University HealthSystem - Evanston Hospital ( Site 1614)
🇺🇸Evanston, Illinois, United States
University of Iowa ( Site 1572)
🇺🇸Iowa City, Iowa, United States
Mercy Health-Paducah Cancer Center ( Site 1623)
🇺🇸Paducah, Kentucky, United States
Our Lady of the Lake RMC-Clinical Research ( Site 1624)
🇺🇸Baton Rouge, Louisiana, United States
Levine Cancer Institute ( Site 1590)
🇺🇸Charlotte, North Carolina, United States
Laura and Isaac Perlmutter Cancer Center ( Site 1582)
🇺🇸New York, New York, United States
University Hospital Cleveland ( Site 1578)
🇺🇸Cleveland, Ohio, United States
University of Cincinnati Medical Center ( Site 1567)
🇺🇸Cincinnati, Ohio, United States
St Francis Cancer Center-Research Office ( Site 1607)
🇺🇸Greenville, South Carolina, United States
The Center For Cancer And Blood Disorders ( Site 1569)
🇺🇸Fort Worth, Texas, United States
The Townsville Hospital ( Site 0107)
🇦🇺Douglas, Queensland, Australia
Monash Health ( Site 0102)
🇦🇺Clayton, Victoria, Australia
A. C. Camargo Cancer Center ( Site 0809)
🇧🇷Sao Paulo, Brazil
Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0307)
🇨🇦Hamilton, Ontario, Canada
Rigshospitalet University Hospital Copenhagen ( Site 1000)
🇩🇰Copenhagen, Hovedstaden, Denmark
S.C.Focus Lab Plus S.R.L ( Site 1703)
🇷🇴Bucuresti, Romania
Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne-ONCOLOGY ( Site 0510)
🇫🇷Clermont-Ferrand, Puy-de-Dome, France
Institut Curie ( Site 0500)
🇫🇷Paris, France
Institut Gustave Roussy ( Site 0505)
🇫🇷Villejuif, Val-de-Marne, France
Seoul National University Bundang Hospital ( Site 1801)
🇰🇷Seongnam, Kyonggi-do, Korea, Republic of
Severance Hospital Yonsei University Health System ( Site 1800)
🇰🇷Seoul, Korea, Republic of
Ajou University Hospital ( Site 1802)
🇰🇷Suwon, Kyonggi-do, Korea, Republic of
Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1702)
🇷🇴Cluj Napoca, Cluj, Romania
S.C. Radiotherapy Center Cluj S.R.L ( Site 1706)
🇷🇴Floresti, Cluj, Romania
S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1704)
🇷🇴Craiova, Dolj, Romania
Centro Oncologico de Galicia ( Site 0706)
🇪🇸A Coruna, Galicia, Spain
Hospital General de Valencia ( Site 0703)
🇪🇸Valencia, Valenciana, Comunitat, Spain
Taichung Veterans General Hospital ( Site 1206)
🇨🇳Taichung, Taiwan
National Taiwan University Hospital ( Site 1200)
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital ( Site 1201)
🇨🇳Taipei, Taiwan
China Medical University Hospital ( Site 1205)
🇨🇳Taichung, Taiwan
Penn State Hershey Medical Center ( Site 1561)
🇺🇸Hershey, Pennsylvania, United States
University of Massachusetts Chan Medical School ( Site 1616)
🇺🇸Worcester, Massachusetts, United States
Jackson Oncology Associates, PLLC-Clinical Trials ( Site 1625)
🇺🇸Jackson, Mississippi, United States
Spitalul Clinic Colțea ( Site 1708)
🇷🇴București, Bucuresti, Romania
Unidade Local de Saude Gaia/Espinho - Hospital Eduardo Santos Silva ( Site 1401)
🇵🇹Vila Nova de Gaia, Porto, Portugal
Administradora Country S.A.S - Clínica del Country ( Site 0407)
🇨🇴Bogotá, Cundinamarca, Colombia
Chang Gung Medical Foundation - Kaohsiung ( Site 1204)
🇨🇳Kaohsiung, Taiwan
Sociedad De Oncologia Y Hematologia Del Cesar ( Site 0404)
🇨🇴Valledupar, Cesar, Colombia
Cabinet Medical Oncomed ( Site 1707)
🇷🇴Timișoara, Timis, Romania
Castle Hill Hospital ( Site 0910)
🇬🇧Cottingham, East Riding Of Yorkshire, United Kingdom
Oncomédica S.A.S ( Site 0409)
🇨🇴Montería, Cordoba, Colombia
National Cheng Kung University Hospital ( Site 1202)
🇨🇳Tainan, Taiwan
Royal Marsden Hospital. ( Site 0901)
🇬🇧Sutton, Surrey, United Kingdom
St. Vincent Frontier Cancer Center ( Site 1507)
🇺🇸Billings, Montana, United States
Instituto de Cancerología ( Site 0408)
🇨🇴Medellin, Antioquia, Colombia
Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen ( Site 0509)
🇫🇷Rouen, Seine-Maritime, France
Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 1400)
🇵🇹Porto, Portugal
Cardiomed SRL Cluj-Napoca ( Site 1701)
🇷🇴Cluj Napoca, Cluj, Romania
Yale-New Haven Hospital-Yale Cancer Center ( Site 1505)
🇺🇸New Haven, Connecticut, United States
Norton Hospital-Norton Cancer Institute - Downtown ( Site 1601)
🇺🇸Louisville, Kentucky, United States
VA Ann Arbor Healthcare System ( Site 1584)
🇺🇸Ann Arbor, Michigan, United States
Medical University of South Carolina ( Site 1579)
🇺🇸Charleston, South Carolina, United States
UF Health ( Site 1554)
🇺🇸Gainesville, Florida, United States