Study of Pembrolizumab/Vibostolimab (MK-7684A) in Combination With Concurrent Chemoradiotherapy Followed by Pembrolizumab/Vibostolimab Versus Concurrent Chemoradiotherapy Followed by Durvalumab in Participants With Stage III Non-small Cell Lung Cancer (MK-7684A-006)

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria

• Has pathologically (histologically or cytologically) confirmed diagnosis of NSCLC.

• Has Stage IIIA, IIIB, or IIIC NSCLC by American Joint Committee on Cancer Version 8

• Is determined to have unresectable, Stage III NSCLC as documented by a multidisciplinary tumor board or by the treating physician in consultation with a thoracic surgeon

• Has no evidence of metastatic disease, indicating Stage IV NSCLC, in whole-body fluorodeoxyglucose (FDG)-positron emission tomography (PET) or FDG-PET/ computed tomography (CT) and CT or magnetic resonance imaging (MRI) scans of diagnostic quality of chest, abdomen, pelvis and brain

• Has measurable disease as defined by RECIST 1.1, with at least 1 lesion being appropriate for selection as a target lesion, as determined by local site investigator/radiology review

• Has not received prior treatment (chemotherapy, targeted therapy, or radiotherapy) for their Stage III NSCLC

• Has provided tumor tissue sample (tissue biopsy [core, incisional, or excisional])

• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 assessed within 7 days prior to the first administration of study intervention

• Has a life expectancy of at least 6 months

Exclusion Criteria

• Has small cell lung cancer (SCLC) or tumors with the presence of small cell elements. Mixed squamous/nonsquamous tumors are eligible

• Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or for breast cancer

• Has received major surgery (with the exception of replacement of vascular access) within 4 weeks before randomization. If the participant had a major operation, the participant must have recovered adequately from the procedure and/or any complications from the operation before starting study intervention

• Is expected to require any other form of antineoplastic therapy, while on study

• Has received colony-stimulating factors (e.g., Granulocyte Colony-Stimulating Factor [G-CSF], Granulocyte Macrophage Colony-Stimulating Factor [GM-CSF], or recombinant erythropoietin) within 28 days prior to the first dose of study intervention

• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention

• Is 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

• 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 medication

• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years

• Has an active autoimmune disease that has required systemic treatment in past 2 years

• Has a 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) infection

• Has a known history of Hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV ribonucleic acid [RNA] qualitative is detected) infection

• Has had an allogenic tissue/solid organ transplant

Pemetrexed-specific Criteria:

• Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 grams per day, for at least 2 days (5 days for long-acting agents [for example, piroxicam]) before, during, and for at least 2 days after administration of pemetrexed

• Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone