Patients with stage I high-risks NSCLC resected tumors will be randomized into the open-label arm A (Intismeran and MK-3475A), in the blinded arm B (Intismeran) or the blinded arm C (placebo).

Intismeran is an mRNA-based INT, IM injection
MK-3475A immunotherapy, SC injection

• Historical diagnosis of pathological stage I (tumor ≤ 4 cm) with at least one of the following high-risk pathological features as assessed locally: a) tumor size > 2 cm, visceral pleural invasion, lymphovascular invastion, high grade histology.
• Has undergone complete surgical resection of the primary NSCLC
• Has not received other prior treatment outside of definitive surgery for current stage I NSCLC
• Documented absence of actionable, activating mutations or rearrangement in EGFR or ALK
• Unequivocal no evidence of disease based on post-surgical radiological assessment by CT within 28 days before randomization
• Has provided tissue sample from recent surgery, meeting the study requirements for PD-L1 and NGS along with the required blood sample.
• HIV-infected participants must have well controlled HIV on ART
• ECOG 0-1
• Undetectable viral load of HCV/HBV
• Adequate organ function

• SCLC/mixed tumors, neuroendocrine tumor with large cell component, sarcomatoid carcinoma, two synchronous primary NSCLC
• Clinical cardiovascular disase
• HIV-infected participants with a history of Kaposi’s sarcoma and/or multicentric Castleman’s disease
• Prior therapy with an anti-PD-1/L1/L2 agent or with an agent directed to another stimulatory or coinhibitory TCR
• Received prior treatment with another INT, cancer vaccine, anticanver therapy, investigational agent or investigational device
• Immunodeficiency or is receiving chronic steroid therapy within 7 days prior to randomization
• Known additional malignancy
• Active autoimmune disease
• History of non-infectious pneumonitis/ILD
• Active infection requiring systemic therapy
• Stem cell/solid organ transplant
• Participants who have not adequately recovered from major surgery