Background: Pembrolizumab (pembro) plus chemotherapy is a standard first-line treatment for patients with metastatic NSCLC without EGFR or ALK genomic alterations regardless of PD-L1 expression. The combination of pembro and vibostolimab, a humanized monoclonal antibody that blocks the interaction between the T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) and its ligands CD112 and CD155, showed antitumor activity and manageable safety in patients with advanced or metastatic NSCLC in the phase 1 MK-7684-001 study. The phase 3 KeyVibe-007 (NCT05226598) study is evaluating the efficacy and safety of pembro and vibostolimab, coformulated as MK-7684A, in combination with chemotherapy versus pembro plus chemotherapy as first-line therapy for metastatic NSCLC. Methods: his randomized, double-blind study is enrolling adults with histologically or cytologically confirmed, previously untreated, stage IV squamous or nonsquamous NSCLC without EGFR mutations or ALK/ROS1 gene rearrangements. Patients must have measurable disease per RECIST v1.1, ECOG PS of 0 or 1, and a tumor tissue sample for PD-L1 assessment. Patients are randomized 1:1 to receive MK-7684A (MK-7684 200 mg + pembro 200 mg) IV or pembro 200 mg IV plus chemotherapy (squamous: carboplatin area under the curve [AUC] 6 mg/mL/min plus paclitaxel 200 mg/m² or nab-paclitaxel 100 mg/m² [days 1, 8, 15]; nonsquamous: pemetrexed 500 mg/m² plus cisplatin 75 mg/m² or carboplatin AUC 5 mg/mL/min) Q3W for 4 cycles followed by MK-7684A or pembro Q3W, per randomized therapy, for up to 31 additional cycles (plus continued pemetrexed maintenance, nonsquamous only) or until PD, unacceptable AEs, investigator decision, or patient withdrawal. Patients with PD after completing first-course treatment may be eligible for up to 17 additional cycles of their randomized therapy (MK-7684A or pembro). Randomization is stratified by ECOG PS (0 vs 1), tumor histology (squamous vs nonsquamous), PD-L1 expression (TPS < 50% vs ≥50%), and region (East Asia vs North America/Western Europe vs rest of world). Dual primary endpoints are PFS per RECIST v1.1 by blinded independent central review (BICR) and OS. Secondary endpoints are ORR and duration of response per RECIST v1.1 by BICR, change from baseline and time to true deterioration in patient-reported outcomes (PROs), and safety. Imaging assessments occur at weeks 6, 12, and 18, then Q9W through week 63 and Q12W thereafter until disease progression, start of new anticancer treatment, withdrawal of consent, or death. PROs are assessed using validated instruments including the EORTC Quality of Life Questionnaire Lung Cancer13 and NSCLC Symptom Assessment Questionnaire. AEs are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Enrollment is ongoing. Clinical trial information: NCT05226598.