Inclusion Criteria:
- Has a histologically or cytologically confirmed diagnosis of Stage IV: M1a, M1b, or
M1c non-small cell lung cancer (NSCLC) per the American Joint Committee on Cancer
(AJCC) Staging Manual, version 8
- Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)
1.1, as determined by the local site assessment
- Has confirmation that epidermal growth factor receptor (EGFR)-, anaplastic lymphoma
kinase (ALK)-, or reactive oxygen species proto-oncogene 1 (ROS1)-directed therapy is
not indicated as primary therapy and absence of ALK and ROS1 gene rearrangements
- Has provided tumor tissue that demonstrates Programmed Cell Death 1 Ligand 1 (PD-L1)
expression in ≥1% of tumor cells as assessed by immunohistochemistry (IHC) at a
central laboratory
- Has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 assessed
within 7 days prior to randomization
- Has a life expectancy of at least 3 months
- A 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 woman of childbearing potential (WOCBP)
- Is 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
- Has adequate organ function
Exclusion Criteria:
- 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
at least 3 years since initiation of that therapy
- Has received prior systemic chemotherapy or other targeted or biological
antineoplastic therapy for their metastatic NSCLC.
- Prior treatment with chemotherapy and/or radiation as part of
neoadjuvant/adjuvant or chemoradiation therapy for nonmetastatic NSCLC is allowed
as long as therapy was completed at least 6 months before the diagnosis of
metastatic NSCLC.
- Participants must have recovered from all AEs due to previous therapies to Grade
≤1 or baseline. Participants with Grade ≤2 neuropathy may be eligible.
Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone
replacement may be eligible.
- Has received prior therapy with an anti-programmed cell death receptor 1 (PD-1),
anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death
receptor ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or
co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4
(CTLA-4), OX-40, CD137)
- Has received previous treatment with another agent targeting the T cell immunoreceptor
with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif (ITIM)
domains (TIGIT) receptor pathway
- Has received radiotherapy within 2 weeks of start of study intervention. Participants
must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system
(CNS) disease
- Has received a live or live-attenuated vaccine within 30 days prior to the first dose
of study intervention. Administration of killed vaccines is allowed
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study intervention
- Has known active or untreated CNS metastases and/or carcinomatous meningitis.
Participants with previously treated brain metastases may participate provided they
are radiologically stable for at least 4 weeks by repeat imaging, clinically stable,
and without requirement of steroid treatment for at least 14 days prior to first dose
of study intervention
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab/vibostolimab or pembrolizumab
and/or any of its excipients
- Has an 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.
- Has a 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 prior to the first dose of study intervention
- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis
- Has a known history of interstitial lung disease. Lymphangitic spread of the NSCLC is
not exclusionary.
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is
required unless mandated by local health authority
- Has a known history of Hepatitis B or known active Hepatitis C virus infection
- Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study