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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04428151
Registration number
NCT04428151
Ethics application status
Date submitted
9/06/2020
Date registered
11/06/2020
Date last updated
23/05/2024
Titles & IDs
Public title
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)
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Scientific 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)
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Secondary ID [1]
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LEAP-009
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Secondary ID [2]
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7902-009
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Squamous Cell Carcinoma of Head and Neck
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0
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Condition category
Condition code
Cancer
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0
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Non melanoma skin cancer
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Cancer
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0
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0
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Kidney
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Cancer
0
0
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0
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Head and neck
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Lenvatinib
Other interventions - Pembrolizumab
Treatment: Drugs - Docetaxel
Treatment: Drugs - Capecitabine
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Cetuximab
Treatment: Drugs - Lenvatinib
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.
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.
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.
Treatment: Drugs: Lenvatinib
20 mg once daily, taken as oral capsules
Other interventions: Pembrolizumab
200 mg 30-minute IV infusion on day 1 of each 21-day cycle
Treatment: Drugs: Docetaxel
75 mg/m^2 administered as an IV infusion on day 1 of each 21-day cycle
Treatment: Drugs: Capecitabine
1250 mg/m^2 twice daily on days 1-14 of each 21-day cycle, taken as oral tablets
Treatment: Drugs: Paclitaxel
80 mg/m^2 administered as an IV infusion on days 1, 8, and 15 of each 21-day cycle
Treatment: Drugs: 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
Treatment: Drugs: Lenvatinib
24 mg once daily, taken as oral capsules
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Objective Response Rate (ORR)
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Assessment method [1]
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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).
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Timepoint [1]
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Up to approximately 4 years
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Secondary outcome [1]
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Progression-Free Survival (PFS)
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Assessment method [1]
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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).
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Timepoint [1]
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Up to approximately 4 years
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Secondary outcome [2]
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Overall Survival (OS)
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Assessment method [2]
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OS is defined as the time from randomization to death due to any cause.
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Timepoint [2]
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Up to approximately 4 years
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Secondary outcome [3]
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Duration of Response (DOR)
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Assessment method [3]
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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.
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Timepoint [3]
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Up to approximately 4 years
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Secondary outcome [4]
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Number of Participants Who Experienced One or More Adverse Events (AEs)
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Assessment method [4]
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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.
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Timepoint [4]
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Up to approximately 4 years
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Secondary outcome [5]
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Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)
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Assessment method [5]
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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.
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Timepoint [5]
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Up to approximately 4 years
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Eligibility
Key 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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
6/08/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
17/02/2027
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Actual
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Sample size
Target
400
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
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Recruitment hospital [1]
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Blacktown Hospital ( Site 0101) - Blacktown
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Mid North Coast Cancer Institute ( Site 0109) - Port Macquarie
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The Townsville Hospital ( Site 0107) - Douglas
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Gallipoli Medical Research Ltd-GMRF CTU ( Site 0105) - Greenslopes
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Royal Adelaide Hospital ( Site 0110) - Adelaide
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Recruitment hospital [6]
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Monash Health ( Site 0102) - Clayton
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Recruitment postcode(s) [1]
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2148 - Blacktown
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2444 - Port Macquarie
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4814 - Douglas
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Recruitment postcode(s) [4]
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4120 - Greenslopes
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Recruitment postcode(s) [5]
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5000 - Adelaide
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Recruitment postcode(s) [6]
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3168 - Clayton
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Recruitment outside Australia
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Bucuresti
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Manchester
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Merck Sharp & Dohme LLC
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Address
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Other collaborator category [1]
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Commercial sector/Industry
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Name [1]
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Eisai Inc.
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Address [1]
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Ethics approval
Ethics application status
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Summary
Brief 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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04428151
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Contacts
Principal investigator
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Medical Director
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Merck Sharp & Dohme LLC
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Toll Free Number
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1-888-577-8839
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[email protected]
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Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04428151
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