- Has a histologically-confirmed or cytologically-confirmed diagnosis of stage IV (M1a,
M1b, or M1c [AJCC 8th edition]) nonsquamous NSCLC.
- Have confirmation that epidermal growth factor receptor- (EGFR-), anaplastic lymphoma
kinase- (ALK-), c-ros oncogene 1 (ROS1), or B isoform of rapidly accelerated
fibrosarcoma (BRAF) directed therapy is not indicated as primary therapy.
Documentation of the absence of tumor activating EGFR mutations, BRAF mutations, ALK
gene rearrangements, and ROS1 gene rearrangements is required.
- Has measurable disease based on RECIST 1.1 as determined by the local site
investigator/radiology assessment. Target lesions situated in a previously irradiated
area are considered measurable if progression has been demonstrated in such lesions.
- Has not received prior systemic treatment for their advanced/metastatic NSCLC.
Participants who received adjuvant or neoadjuvant therapy are eligible if the
adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development
of metastatic disease.
- Have provided sufficient evaluable Stage IV, archival, solid tumor tissue sample or
newly obtained core or excisional biopsy of a tumor lesion (that was not previously
irradiated) for biomarker analysis (Fine Needle Aspiration [FNA] samples will not be
accepted). Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to
slides. Newly obtained biopsies are preferred to archived tissue.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within
10 days prior to the first dose of study treatment.
- A male participant must agree to use contraception through the end of treatment and
for at least 120 days, and refrain from donating sperm during this period.
- A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and if participant is a woman of childbearing potential (WOCBP), agrees
to follow the contraceptive guidance as provided in the protocol through the end of
- Has adequate organ function.
- Has provided blood for Circulating Free DNA (cfDNA) analysis that has been received
and determined to be of sufficient quality and quantity by the designated laboratory
for the primary endpoint.
- Has predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by
the predominant cell type.
- Has small cell elements present in NSCLC tumor.
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment
- Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI)
obstruction, peritoneal carcinomatosis.
- Has a known history of prior malignancy except if the participant has undergone
potentially curative therapy with no evidence of that disease recurrence for 2 years
since initiation of that therapy.
- Has symptomatic ascites or pleural effusion. A participant who is clinically stable
following treatment for these conditions (including therapeutic thoraco- or
paracentesis) is eligible.
- If participant received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting study
- Has received prior 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
- Has received prior therapy with a multiple programmed cell death 1 (PD-1)/ (PD-1)
receptor/programmed cell death ligand 1 (PD-L1) receptor inhibitor.
- Is expected to require any other form of antineoplastic therapy while on study
(including maintenance therapy with another agent for NSCLC, radiation therapy, and/or
- Has received a live vaccine within 30 days prior to treatment.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
or to another monoclonal antibody.
- Has a known sensitivity to any component of cisplatin, carboplatin or pemetrexed.
- Has active autoimmune disease that has required systemic treatment in past 2 years
(i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive
- Is on chronic systemic steroids. Participants with asthma that require intermittent
use of bronchodilators, inhaled steroids, or local steroid injections would not be
excluded from the study.
- Is unable or unwilling to take folic acid or vitamin B12 supplementation.
- 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
- 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 the first dose of study drug.
- Has a known additional malignancy that is progressing or has required active treatment
within the past 2 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma,
cervical cancer in situ) that have undergone potentially curative therapy are not
- Has known active central nervous system (CNS) metastases and/or carcinomatous
- Has a history of (non-infectious) pneumonitis that required steroids or has current
- 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 (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the participant's
participation for the full duration of the study, or is not in the best interest of
the participant to participate, in the opinion of the treating investigator.
- Has a known psychiatric or substance abuse disorder that would interfere with
cooperating with the requirements of the study.
- 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 intervention.
- Has had an allogenic tissue/solid organ transplant.