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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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ClinicalTrials.gov Identifier: NCT04428151
Recruitment Status : Recruiting
First Posted : June 11, 2020
Last Update Posted : November 29, 2021
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE June 9, 2020
First Posted Date  ICMJE June 11, 2020
Last Update Posted Date November 29, 2021
Actual Study Start Date  ICMJE August 6, 2020
Estimated Primary Completion Date August 18, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2020)
Objective Response Rate (ORR) [ Time Frame: Up to approximately 4 years ]
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2020)
  • Progression-Free Survival (PFS) [ Time Frame: Up to approximately 4 years ]
    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).
  • Overall Survival (OS) [ Time Frame: Up to approximately 4 years ]
    OS is defined as the time from randomization to death due to any cause.
  • Duration of Response (DOR) [ Time Frame: Up to approximately 4 years ]
    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.
  • Number of Participants Who Experienced One or More Adverse Events (AEs) [ Time Frame: Up to approximately 4 years ]
    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.
  • Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE) [ Time Frame: Up to approximately 4 years ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Squamous Cell Carcinoma of Head and Neck
Intervention  ICMJE
  • Drug: Lenvatinib
    20 mg once daily, taken as oral capsules
    Other Names:
    • LENVIMA®
    • MK-7902
    • E7080
  • Biological: Pembrolizumab
    200 mg 30-minute IV infusion on day 1 of each 21-day cycle
    Other Names:
    • KEYTRUDA®
    • MK-3475
    • SCH 900475
  • Drug: Docetaxel
    75 mg/m^2 administered as an IV infusion on day 1 of each 21-day cycle
    Other Name: TAXOTERE®
  • Drug: Capecitabine
    1250 mg/m^2 twice daily on days 1-14 of each 21-day cycle, taken as oral tablets
    Other Name: Xeloda®
  • Drug: Paclitaxel
    80 mg/m^2 administered as an IV infusion on days 1, 8, and 15 of each 21-day cycle
    Other Name: 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 Name: ERBITUX®
  • Drug: Lenvatinib
    24 mg once daily, taken as oral capsules
    Other Names:
    • LENVIMA®
    • MK-7902
    • E7080
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Lenvatinib
    • Biological: Pembrolizumab
  • 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.
    Interventions:
    • Drug: Docetaxel
    • Drug: Capecitabine
    • Drug: Paclitaxel
    • Drug: Cetuximab
  • 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.
    Intervention: Drug: Lenvatinib
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 9, 2020)
400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 18, 2024
Estimated Primary Completion Date August 18, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Australia,   Canada,   Denmark,   France,   Israel,   Korea, Republic of,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04428151
Other Study ID Numbers  ICMJE 7902-009
LEAP-009 ( Other Identifier: Merck )
E7080-G000-228 ( Other Identifier: Eisai )
MK-7902-009 ( Other Identifier: Merck )
2019-000569-19 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Eisai Inc.
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP