Inclusion Criteria:
- Has a histologically or cytologically confirmed diagnosis of NSCLC.
- Has Stage IV NSCLC (American Joint Committee on Cancer [AJCC]).
- 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 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.
- 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 treatment.
- 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.
