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], version 8 or current version), 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 archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion (not previously irradiated).
• 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.
• Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
• Male participants must agree for at least 7 days after the last dose of lenvatinib/matching placebo and up to 180 days after the last dose of chemotherapeutic agents to:
• Refrain from donating sperm PLUS either:
• Be abstinence 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 azoopsermic (vasectomized or secondary to medical cause) as detailed below:
• 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 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.

Note: 7 days after lenvatinib/matching placebo is stopped, if the participant is on pembrolizumab only and is greater than 180 days post chemotherapy, no male contraception measures are needed.

• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• 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 WOCBP OR
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of 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 intratumoral caviations, encasement, or invasion of a major blood vessel. Additionally, the degree of proximity to major blood vessels should be considered for exclusion because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib-therapy. (In the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the su