Inclusion Criteria:

- A histologically or cytologically confirmed diagnosis of Stage IV squamous or
non-squamous NSCLC.
- Has not received prior systemic treatment for metastatic NSCLC.
- Has measurable disease based on RECIST 1.1, as determined by the local site
assessment.
- Has a life expectancy of at least 3 months.
- Males: Use contraception unless confirmed to be azoospermic; Females: Women of
childbearing potential use highly effective contraceptive method.

Exclusion Criteria:

- Known additional malignancy that is progressing or has required active treatment
within the past 3 years.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Severe hypersensitivity to vibostolimab, pembrolizumab, chemotherapy components,
and/or any of its excipients.
- 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 before the first dose of study medication.
- Active autoimmune disease that has required systemic treatment in past 2 years (ie,
with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement
therapy for adrenal or pituitary insufficiency) is not considered a form of systemic
treatment and is allowed.
- History of (noninfectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus (HIV), Hepatitis B or/and
Hepatitis C virus.
- Received prior systemic anticancer therapy for metastatic disease.
- Received a live or live attenuated vaccine within 30 days before the first dose of
study intervention. Administration of killed vaccines are allowed.
- History of allogeneic tissue/solid organ transplant.
- Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs),
other than an aspirin dose ≤1.3 g/day, for a 5-day period (8-day period for
long-acting agents, such as piroxicam).
- Is unable or unwilling to take folic acid or vitamin B12 supplementation.
- Currently participating in or has participated in a study of an investigational agent
or has used an investigational device within 4 weeks before the first dose of study
intervention.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 2/19/2024. Questions regarding updates should be directed to the study team contact.