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)

Researchers are looking for new ways to treat people with locally advanced non-small cell lung cancer (NSCLC). The goal of this study is to learn if people who receive the combination of vibostolimab and pembrolizumab (MK-7684A) live longer without the cancer getting worse and live longer overall than people who receive durvalumab.

As of protocol amendment 4, participants receiving combination vibostolimab and pembrolizumab (MK-7684A) discontinued treatment due to lack of efficacy observed in other MK-7684A studies, and are given the option to transition to durvalumab therapy.

Eligibility Criteria:
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