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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 : October 8, 2020
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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 pembrolizumab + lenvatinib 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.

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of Head and Neck Drug: Pembrolizumab Drug: Lenvatinib Drug: Docetaxel Drug: Capecitabine Drug: Paclitaxel Drug: Cetuximab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : August 6, 2020
Estimated Primary Completion Date : August 18, 2024
Estimated Study Completion Date : August 18, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pembrolizumab + Lenvatinib
Participants will be treated with the combination of pembrolizumab (200 mg 30-minute intravenous (IV) infusion on day 1 of each 21-day cycle for 35 cycles), plus lenvatinib (once daily 20 mg oral dose) 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.
Drug: Pembrolizumab
200 mg 30-minute IV infusion on day 1 of each 21-day cycle
Other Names:
  • KEYTRUDA®
  • MK-3475
  • SCH 900475

Drug: Lenvatinib
20 mg once daily, taken as oral capsules
Other Names:
  • LENVIMA®
  • MK-7902
  • E7080

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.
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®

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.
Drug: Lenvatinib
24 mg once daily, taken as oral capsules
Other Names:
  • LENVIMA®
  • MK-7902
  • E7080




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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).

  2. Overall Survival (OS) [ Time Frame: Up to approximately 4 years ]
    OS is defined as the time from randomization to death due to any cause.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 (eg, 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 (Arm2).
    • 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
  • 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 that required systemic steroids, or 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 condition or procedure that, in the opinion of the investigator, 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
  • Difficulty swallowing capsules or ingesting a suspension either orally, by a nasogastric (NG) tube, or by a gastrostomy 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
  • Received a live vaccine within 30 days of planned start of study intervention
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04428151


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Eisai Inc.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04428151    
Other Study ID Numbers: 7902-009
LEAP-009 ( Other Identifier: Merck )
E7080-G000-228 ( Other Identifier: Eisai )
MK-7902-009 ( Other Identifier: Merck )
2019-000569-19 ( EudraCT Number )
First Posted: June 11, 2020    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Paclitaxel
Docetaxel
Capecitabine
Pembrolizumab
Cetuximab
Lenvatinib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Immunological
Protein Kinase Inhibitors
Enzyme Inhibitors