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A Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First Line (1L) Intervention in a Programmed Cell Death-ligand 1 (PD-L1) Selected Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (LEAP-010) (MK-7902-010)

NCT04199104

Description:

This is a study of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) as a first line intervention in a PD-L1 selected population with participants with recurrent or metastatic head and neck squamous cell carcinoma. Hypotheses include: - Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR). - Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR. - Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to overall survival (OS).

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First Line (1L) Intervention in a Programmed Cell Death-ligand 1 (PD-L1) Selected Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (LEAP-010) (MK-7902-010)
  • Official Title: A Phase 3, Randomized, Placebo-controlled, Double-blind Clinical Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) to Evaluate the Safety and Efficacy of Pembrolizumab and Lenvatinib as 1L Intervention in a PD-L1 Selected Population of Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (LEAP-010).

Clinical Trial IDs

  • ORG STUDY ID: 7902-010
  • SECONDARY ID: MK-7902-010
  • SECONDARY ID: LEAP-10
  • SECONDARY ID: 2019-003717-34
  • NCT ID: NCT04199104

Conditions

  • Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
LenvatinibE7080, MK-7902, LENVIMA®Pembrolizumab with Lenvatinib
PembrolizumabMK-3475, Keytruda®Pembrolizumab with Lenvatinib
PlaceboPembrolizumab with Placebo

Purpose

This is a study of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) as a first line intervention in a PD-L1 selected population with participants with recurrent or metastatic head and neck squamous cell carcinoma. Hypotheses include: - Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR). - Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR. - Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to overall survival (OS).

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab with LenvatinibExperimentalParticipants receive lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.
  • Lenvatinib
  • Pembrolizumab
Pembrolizumab with PlaceboActive ComparatorParticipants receive lenvatinib-matching placebo orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months).
  • Pembrolizumab
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Has histologically confirmed diagnosis of R/M HNSCC that is considered incurable by
             local therapies.

        Note: Participants with newly-diagnosed HNSCC must be M1/Stage IV.

          -  Has a primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx.

        Note: Primary tumor site of nasopharynx (any histology) or unknown primary tumor are not
        eligible.

          -  Male participants agree to use approved contraception during the treatment period for
             at least 30 days after the last dose of lenvatinib/placebo, or refrain from
             heterosexual intercourse during this period

          -  Female participants are not pregnant or breastfeeding, and are not a woman of
             childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during
             the treatment period (or 14 days prior to the initiation of study treatment for oral
             contraception) and for at least 120 days post pembrolizumab, or 30 days post
             lenvatinib/placebo, whichever occurs last

          -  Has measurable disease per RECIST 1.1 as assessed by BICR. Note: Lesions situated in a
             previously irradiated area are considered measurable if progression has been
             demonstrated in such lesions.

          -  Participants with oropharyngeal cancer must have results from testing of human
             papillomavirus HPV status.

          -  Has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.

          -  Has adequately controlled blood pressure with or without antihypertensive medications.

          -  Has adequate organ function.

        Exclusion Criteria:

          -  Has a history of any contraindication or has a severe hypersensitivity to any
             components of pembrolizumab (≥Grade 3) or lenvatinib.

          -  Has pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.

          -  Has a history of a gastrointestinal condition or procedure that, in the opinion of the
             investigator, may affect oral study drug absorption.

          -  Has clinically significant cardiovascular impairment within 12 months of the first
             dose of study drug, such as history of congestive heart failure greater than New York
             Heart Association (NYHA) Class II, unstable angina, myocardial infarction or
             cerebrovascular accident/transient ischemic attack (TIA)/stroke, cardiac
             revascularization, or cardiac arrhythmia associated with hemodynamic instability.

          -  Has disease that is suitable for local therapy administered with curative intent.

          -  Had PD within 6 months of completion of curatively intended systemic treatment for
             locoregionally advanced HNSCC.

          -  Has had major surgery within 3 weeks prior to first dose of study interventions.

          -  Has difficulty swallowing capsules or ingesting a suspension either orally or by a
             nasogastric (NG) tube.

          -  Has received prior therapy with lenvatinib or pembrolizumab.

          -  Received last dose of systemic therapy for locoregionally advanced disease less than 6
             months prior to signing consent.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
             CTLA-4, OX-40, CD137).

          -  Has received prior systemic anticancer therapy including investigational agents within
             4 weeks prior to randomization.

          -  Has received prior radiotherapy within 2 weeks of start of study intervention.

          -  Has received a live vaccine within 30 days prior to the first dose of study drug.

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

          -  Has a 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 the first dose of study drug.

          -  Has a known additional malignancy that is progressing or has required active treatment
             within the past 3 years.

        Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the
        skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have
        undergone potentially curative therapy are not excluded.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

          -  Has an active autoimmune disease that has required systemic treatment in past 2 years
             (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency) is not considered a form
             of systemic treatment and is allowed.

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  Has a known history of human immunodeficiency virus (HIV) infection.

          -  Has a known history of hepatitis B (defined as HBsAg reactive) or known active
             hepatitis C virus (defined as HCV ribonucleic acid (RNA) [qualitative] is detected)
             infection.

          -  Has a known history of active tuberculosis (TB; Bacillus tuberculosis).

          -  Is pregnant or breastfeeding or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of study intervention.

          -  Has had an allogenic tissue/solid organ transplant.

          -  Has a known psychiatric or substance abuse disorder that would interfere with the
             participant's ability to cooperate with the requirements of the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR).
Time Frame:Up to approximately 24 months
Safety Issue:
Description:ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experience a CR or PR based on modified RECIST 1.1 will be presented.

Secondary Outcome Measures

Measure:Duration of Response (DOR)
Time Frame:Up to approximately 44 months
Safety Issue:
Description:For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death.
Measure:Number of Participants Who Experienced an Adverse Event (AE)
Time Frame:Up to approximately 44 months
Safety Issue:
Description:An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Measure:Number of Participants Who Discontinued Study Drug Due to an AE
Time Frame:Up to approximately 44 months
Safety Issue:
Description:An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • head and neck squamous cell carcinoma
  • pembrolizumab
  • lenvatinib
  • PD-L1

Last Updated

February 13, 2020