Safety and Efficacy Study of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-7902-006/E7080-G000-315/LEAP-006)

Inclusion Criteria:

- Histologically or cytologically confirmed diagnosis of Stage IV (American Joint
Committee on Cancer [AJCC], nonsquamous NSCLC.

- Confirmation that Epidermal Growth Factor Receptor (EGFR), ALK Receptor Tyrosine
Kinase (ALK), or ROS1 Receptor Tyrosine Kinase (ROS1)-directed therapy is not
indicated as primary treatment (documentation of absence of tumor-activating EGFR
mutations AND absence of ALK and ROS1 gene rearrangements OR presence of a Kirsten Rat
Sarcoma (KRAS) gene mutation).

- Have measurable disease based on RECIST 1.1. Note: Lesions that appear measurable, but
are situated in a previously irradiated area, can be considered measurable (eligible
for selection as target lesions) if they have shown documented growth since the
completion of radiation.

- Provided an evaluable archival tumor tissue sample or newly obtained core or
excisional biopsy of a tumor lesion (that was not previously irradiated) for central
PD-L1 testing.

- Life expectancy of at least 3 months.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days
prior to the first dose of study intervention but before randomization.

- Male participants must agree to use contraception during the treatment period and for
at least 120 days after the last dose of pembrolizumab and/or lenvatinib/matching
placebo and up to 180 days after the last dose of chemotherapeutic agents. A male
participant must also agree to the following: 1) abstinence from heterosexual
intercourse as their preferred and usual lifestyle (abstinent on a long term and
persistent basis) and agree to remain abstinent, OR 2) agree to use a male condom plus
partner use of an additional contraceptive method when having penile-vaginal
intercourse with a woman of childbearing potential (WOCBP) who is not currently
pregnant, unless confirmed to be azoospermic (vasectomized or secondary to medical
cause). Note: Men with a pregnant or breastfeeding partner must agree to remain
abstinent from penile-vaginal intercourse or use a male condom during each episode of
penile-vaginal penetration.

- Female participant is eligible to participate if she is not pregnant or breastfeeding,
and at least one of the following conditions applies: 1) not a WOCBP OR 2) 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 after the last dose of study
intervention.

- Adequate organ function.

- 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 prior to randomization. Note: Participants must not have a history of
uncontrolled or poorly-controlled hypertension, defined as >150/90 mm Hg for >4 weeks
despite standard medical management.

Exclusion Criteria:

- Known untreated central nervous system (CNS) metastases and/or carcinomatous
meningitis. Participants with previously treated brain metastases may participate
provided they are radiologically stable, clinically stable, and have not required
steroids for at least 14 days prior to the first dose of study intervention.

- History of (noninfectious) pneumonitis that required systemic steroids or current
pneumonitis/interstitial lung disease.

- Radiographic evidence of major blood vessel invasion/infiltration.

- Known history of an additional malignancy, except if the participant has undergone
potentially curative therapy with no evidence of that disease recurrence for at least
3 years since initiation of that therapy. Note: The time requirement also 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.

- Active autoimmune disease that has required systemic treatment in the 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, etc.) is allowed.

- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses
exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive
therapy within 7 days prior the first dose of study intervention.

- Has had allogeneic tissue/solid organ transplant.

- Known history of human immunodeficiency virus (HIV) infection. HIV testing is not
required unless mandated by the local health authority.

- Known history of Hepatitis B. No testing for Hepatitis B or Hepatitis C is required
unless mandated by the local health authority.

- History of a gastrointestinal condition or procedure that in the opinion of the
investigator may affect oral drug absorption.

- Active hemoptysis (at least 0.5 teaspoon of bright red blood) within 2 weeks prior to
the first dose of study intervention.

- Significant cardiovascular impairment within 12 months prior to the first dose of
study intervention, including history of congestive heart failure greater than New
York Heart Association (NYHA) Class II, unstable angina, myocardial infarction,
cerebrovascular accident (CVA)/stroke, or cardiac arrhythmia associated with
hemodynamic instability.

- Known history of active tuberculosis.

- Active infection requiring systemic therapy.

- Has not recovered adequately from any toxicity and/or complication from major surgery
prior to the first dose of study intervention.

- Previously had a severe hypersensitivity reaction to treatment with a monoclonal
antibody or has a known sensitivity to any component of lenvatinib or pembrolizumab,
or as applicable, carboplatin, cisplatin, or pemetrexed.

- 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 pembrolizumab and/or lenvatinib/matching placebo and up to 180
days after last dose of chemotherapeutic agents.

- Received prior systemic chemotherapy or other targeted or biological antineoplastic
therapy for their metastatic NSCLC. Note: Prior treatment with chemotherapy and/or
radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was
completed at least 6 months prior to the diagnosis of metastatic NSCLC.

- Received prior treatment with pembrolizumab or any other anti-programmed cell death
(PD)-1, anti-PD-L1, anti-PD-L2 agent, with lenvatinib or any other receptor tyrosine
kinase inhibitor (RTKi), or with an agent directed to another stimulatory or
co-inhibitory T cell receptor.

- Received radiotherapy within 14 days prior to the first dose of study intervention or
received lung radiation therapy of >30 Gy within 6 months prior to the first dose of
study intervention. Note: Participants must have recovered from all radiation-related
toxicities to Grade ≤1, not required corticosteroids, and not have had radiation
pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of
radiotherapy) to non-CNS disease.

- Received systemic steroid therapy (in doses exceeding 10 mg daily of prednisone
equivalent) within 7 days prior to the first dose of study intervention.

- Received a live vaccine within 30 days prior to the first dose of study intervention.

- Currently participating and receiving study therapy 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.

- History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's
opinion, is clinically meaningful.

- Left ventricular ejection fraction (LVEF) below the institutional (or local
laboratory) normal range as determined by multigated acquisition scan (MUGA) or
echocardiogram (ECHO).