A randomized, parallel-group, multisite, double-blind phase 3 safety and efficacy study to evaluate the addition of V940 (a mRNA-based INT) to adjuvant pembrolizumab in participants with resectable stage II-IIIB (N2) NSCLC who did not achieve a pCR after neoadjuvant pembrolizumab with platinum-doublet chemotherapy followed by surgery.

Experimental: Pembrolizumab + Intismeran autogene
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via intravenous (IV) infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC] 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS intismeran autogene 1 mg via intramuscular (IM) injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
Interventions:
Biological: Pembrolizumab
Drug: Cisplatin
Drug: Carboplatin
Drug: Pemetrexed
Drug: Gemcitabine
Drug: Paclitaxel
Biological: Intismeran autogene

Active Comparator: Pembrolizumab + Placebo
For neoadjuvant treatment, participants will receive pembrolizumab 200 mg via IV infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m^2 or carboplatin AUC 5 or 6 mg/mL/min, pemetrexed 500 mg/m^2, gemcitabine 1000 mg/m^2, paclitaxel 175 mg/m^2 or 200 mg/m^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to ~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS matching placebo via IM injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to ~42 weeks).
Interventions:
Biological: Pembrolizumab
Drug: Cisplatin
Drug: Carboplatin
Drug: Pemetrexed
Drug: Gemcitabine
Drug: Paclitaxel
Other: Placebo

• Has histologically/cytologically confirmed diagnosis of previously untreated and pathologically confirmed resectable Stage II, IIIA, or IIIB (N2) non-small cell lung cancer (NSCLC) [American Joint Committee on Cancer (AJCC) 8th Edition]
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study intervention
• Participants who have not achieved a pathological complete response (pCR) following completion of neoadjuvant chemotherapy and pembrolizumab followed by surgery will be eligible
• Confirmation that epidermal growth factor receptor (EGFR)-directed therapy is not indicated as primary therapy (documentation of absence of tumor-activating EGFR mutations [eg, DEL19 or L858R])
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy (ART)
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening

• Diagnosis of SCLC or, for mixed tumors, presence of small cell elements, or has a neuroendocrine tumor with large-cell components, or a sarcomatoid carcinoma, or a pancoast tumor
• Documentation by local test report indicating presence of anaplastic lymphoma kinase (ALK) gene rearrangements
• Received prior neoadjuvant therapy for their current NSCLC diagnosis
• Received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell-death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein [CTLA-4], OX-40, CD137)
• Received prior systemic anticancer therapy including investigational agents other than what is specified in this protocol
• Received prior treatment with a cancer vaccine
• Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention