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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04428151




Registration number
NCT04428151
Ethics application status
Date submitted
9/06/2020
Date registered
11/06/2020
Date last updated
7/05/2021

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)
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)
Secondary ID [1] 0 0
LEAP-009
Secondary ID [2] 0 0
7902-009
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Squamous Cell Carcinoma of Head and Neck 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
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

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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).
Timepoint [1] 0 0
Up to approximately 4 years
Secondary outcome [1] 0 0
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).
Timepoint [1] 0 0
Up to approximately 4 years
Secondary outcome [2] 0 0
Overall Survival (OS) - OS is defined as the time from randomization to death due to any cause.
Timepoint [2] 0 0
Up to approximately 4 years
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Up to approximately 4 years
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Up to approximately 4 years
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Up to approximately 4 years

Eligibility
Key inclusion criteria
- Histologically 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.

- Contraceptive use by women should be consistent with local regulations regarding
the methods of contraception for those participating in clinical studies.

- Adequately controlled blood pressure (BP) with or without antihypertensive
medications.

- Adequate organ function.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Carcinoma of the nasopharynx, salivary gland, unknown primary origin, or nonsquamous
histologies as primary tumors.

- 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 hepatitis B or known active hepatitis C virus.

- 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.

- 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.

- Currently participating in or has participated in a study of an investigational agent
and received study therapy or used an investigational device within 4 weeks prior to
the first dose of study intervention.

- Known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Blacktown Hospital ( Site 0101) - Blacktown
Recruitment hospital [2] 0 0
Mid North Coast Cancer Institute ( Site 0109) - Port Macquarie
Recruitment hospital [3] 0 0
Gallipoli Medical Research Foundation-GMRF CTU ( Site 0105) - Brisbane
Recruitment hospital [4] 0 0
The Townsville Hospital ( Site 0107) - Douglas
Recruitment hospital [5] 0 0
Monash Health ( Site 0102) - Clayton
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [3] 0 0
4120 - Brisbane
Recruitment postcode(s) [4] 0 0
4814 - Douglas
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Mississippi
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oklahoma
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
Canada
State/province [21] 0 0
Alberta
Country [22] 0 0
Canada
State/province [22] 0 0
British Columbia
Country [23] 0 0
Denmark
State/province [23] 0 0
Hovedstaden
Country [24] 0 0
France
State/province [24] 0 0
Bouches-du-Rhone
Country [25] 0 0
France
State/province [25] 0 0
Languedoc-Roussillon
Country [26] 0 0
France
State/province [26] 0 0
Seine-Maritime
Country [27] 0 0
France
State/province [27] 0 0
Val-de-Marne
Country [28] 0 0
France
State/province [28] 0 0
Paris
Country [29] 0 0
Israel
State/province [29] 0 0
Tel Aviv
Country [30] 0 0
Israel
State/province [30] 0 0
Haifa
Country [31] 0 0
Israel
State/province [31] 0 0
Jerusalem
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Kyonggi-do
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Seoul
Country [34] 0 0
Spain
State/province [34] 0 0
Barcelona
Country [35] 0 0
Spain
State/province [35] 0 0
Madrid, Comunidad De
Country [36] 0 0
Spain
State/province [36] 0 0
Valenciana, Comunitat
Country [37] 0 0
Spain
State/province [37] 0 0
Malaga
Country [38] 0 0
Taiwan
State/province [38] 0 0
Taoyuan
Country [39] 0 0
Taiwan
State/province [39] 0 0
Kaohsiung
Country [40] 0 0
Taiwan
State/province [40] 0 0
Tainan
Country [41] 0 0
Taiwan
State/province [41] 0 0
Taipei
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Glasgow City
Country [43] 0 0
United Kingdom
State/province [43] 0 0
London, City Of
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Somerset
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Surrey
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Eisai Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/show/NCT04428151
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04428151