Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) in Adults With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Treatment-naïve Nonsmall Cell Lung Cancer (NSCLC) (MK-7902-007/E7080-G000-314/LEAP-007)
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pembrolizumab; Lenvatinib; Placebo for lenvatinib
Intervention description: IV infusion; oral capsule; oral capsule
Intervention MeSH terms: Pembrolizumab; Lenvatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 623.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: programmed cell death 1 (PD-1, PD1); programmed cell death-ligand 1 (PD-L1, PDL1); programmed cell death-ligand 2 (PD-L2, PDL2)

Summary:

      The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475)
      combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for
      lenvatinib) in treatment-naïve adults with no prior systemic therapy for their metastatic
      non-small cell lung cancer (NSCLC) whose tumors have a programmed cell death-ligand 1 (PD-L1)
      Tumor Proportion Score (TPS) greater than or equal to 1%.

      The primary study hypotheses are that: 1) the combination of pembrolizumab and lenvatinib is
      superior to pembrolizumab alone as assessed by Progression-free Survival (PFS) per Response
      Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1); and 2) the combination of
      pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Overall
      Survival (OS).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has a histologically or cytologically confirmed diagnosis of NSCLC.

          -  Has Stage IV NSCLC (American Joint Committee on Cancer [AJCC 8th edition]).

          -  Has measurable disease based on RECIST 1.1.

          -  Has tumor tissue that demonstrates programmed cell death-ligand 1 (PD-L1) expression
             in ≥1% of tumor cells (Tumor Proportion Score [TPS] ≥1%) as assessed by
             immunohistochemistry (IHC) 22C3 pharmDx assay (Dako North America, Inc.) at a central
             laboratory.

          -  Has a life expectancy of ≥3 months.

          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7
             days before the first dose of study treatment but before randomization.

          -  Male participants must agree to the following during the treatment period and for ≥7
             days after the last dose of lenvatinib/matching placebo: 1) Be abstinent from
             heterosexual intercourse as their preferred and usual lifestyle and agree to remain
             abstinent, OR 2) Must agree to use contraception unless confirmed to be azoospermic
             (vasectomized or secondary to medical cause).

          -  Female participants are eligible to participate if not pregnant or breastfeeding, and
             ≥1 of the following applies: 1) Is not a woman of child-bearing potential (WOCBP), OR
             2) Is a WOCBP and is using a highly effective contraceptive method that has a low user
             dependency, or be abstinent from heterosexual intercourse as their preferred and usual
             lifestyle during the treatment period and for ≥120 days post pembrolizumab or ≥30 days
             post lenvatinib/matching placebo, whichever occurs last.

          -  Has adequately controlled blood pressure (BP) with or without antihypertensive
             medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications
             within 1 week before randomization.

          -  Has adequate organ function.

        Exclusion Criteria:

          -  Has known untreated central nervous system metastases and/or carcinomatous meningitis.

          -  Has active hemoptysis (at least 0.5 teaspoon of bright red blood) within 2 weeks prior
             to the first dose of study intervention.

          -  Has radiographic evidence of intratumoral cavitations, encasement, or invasion of a
             major blood vessel.

          -  Has a known history of an additional malignancy, except if the participant has
             undergone potentially curative therapy with no evidence of that disease recurrence for
             ≥3 years since initiation of that therapy. (Note: The time requirement does not apply
             to participants who underwent successful definitive resection of basal cell carcinoma
             of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ
             cervical cancer, or other in situ cancers.)

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment and is allowed.

          -  Has had an allogeneic tissue/solid organ transplant.

          -  Has a known history of human immunodeficiency virus (HIV) infection.

          -  Has a history of (noninfectious) pneumonitis that required systemic steroids or
             current pneumonitis/interstitial lung disease.

          -  Has a known history of hepatitis B or known active hepatitis C virus infection.

          -  Has a history of a gastrointestinal condition or procedure that in the opinion of the
             investigator may affect oral study drug absorption.

          -  Has significant cardiovascular impairment within 12 months of the first dose of study
             treatment, such as a history of congestive heart failure greater than New York Heart
             Association Class II, unstable angina, myocardial infarction, cerebrovascular
             accident/stroke, or cardiac arrhythmia associated with hemodynamic instability.

          -  Has not recovered adequately from any toxicity and/or complications from major surgery
             before starting study treatment.

          -  Has a known history of active tuberculosis (TB).

          -  Has an active infection requiring systemic therapy.

          -  Has previously had a severe hypersensitivity reaction to treatment with a monoclonal
             antibody or has a known sensitivity or intolerance to any component of lenvatinib or
             pembrolizumab.

          -  Has received prior systemic chemotherapy or other targeted or biological
             antineoplastic therapy for their metastatic NSCLC.

          -  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.
             cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor
             superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9
             [CD137]) or has received lenvatinib as monotherapy or in combination with anti-
             programmed cell death protein (anti-PD-1) agents.

          -  Has received radiotherapy within 14 days before the first dose of study treatment or
             received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose
             of study treatment. (Note: Participants must have recovered from all radiation-related
             toxicities to ≤Grade 1, not require corticosteroids, and not have had radiation
             pneumonitis.)

          -  Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive
             therapy within 7 days before the first dose of study treatment.

          -  Is receiving systemic steroid therapy (doses >10 mg daily of prednisone equivalent)
             within 7 days before the first dose of study treatment.

          -  Has received a live or attenuated vaccine within 30 days before the first dose of
             study treatment.

          -  Has had major surgery within 3 weeks prior to first dose of study treatment

          -  Has pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula.