A Study of Intismeran Autogene (V940)/Placebo + Pembrolizumab and Chemotherapy in Metastatic Squamous Non-Small Cell Lung Cancer (V940-013)

Researchers want to know if intismeran autogene (the study treatment) given with pembrolizumab and chemotherapy can treat metastatic treatment-naive squamous non-small cell lung cancer (NSCLC). Intismeran autogene is designed to help a person's immune system attack their specific cancer. The goal of this study is to learn if people who receive intismeran autogene with pembrolizumab and chemotherapy live longer overall and without the cancer growing or spreading compared to people who receive placebo with pembrolizumab and chemotherapy. A placebo looks like the study treatment but has no study treatment in it. Using a placebo helps researchers better understand the effects of the study treatment.

Inclusion Criteria: Inclusion Criteria include, but are not limited to: * Has a histologically or cytologically confirmed diagnosis of squamous non-small cell lung cancer (NSCLC) (Stage IV: M1a, M1b, M1c1, M1c2, AJCC Staging Manual, Version 9). NOTE: Mixed tumors will be characterized by the predominant cell type; however, small cell elements are not permitted. * Has measurable disease per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the local site investigator/radiology * Has provided a tissue sample that is collected either at the time of or after the diagnosis of metastatic disease AND is from a site not previously irradiated * Adverse events (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART) * Hepatitis B surface antigen (HBsAg) positive participants 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. NOTE: Participants must have completed curative antiviral therapy at least 4 weeks prior to randomization * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization * Has a life expectancy of at least 3 months * Has adequate organ function Exclusion Criteria: Exclusion Criteria include, but are not limited to: * Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has received prior treatment with a cancer vaccine, including another personalized cancer vaccine (PCV) * Has received prior systemic anticancer therapy for their metastatic NSCLC * Has received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell death ligand 2 (anti-PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor. NOTE: Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent in the neoadjuvant or adjuvant setting for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC * Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids * Has received radiation therapy to the lung that is \>30 gray within 6 months of start of study intervention * Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed * Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration * 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 intervention * Has known additional malignancy that is progressing or has required active treatment within the past 3 years * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has severe hypersensitivity (≥Grade 3) to V940, pembrolizumab, or any of the protocol allowed chemotherapy agents and/or any of their excipients * Has active autoimmune disease that has required systemic treatment in the past 2 years * Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease * Has active infection requiring systemic therapy * Has a history of stem cell/solid organ transplant * Has not adequately recovered from major surgery or has ongoing surgical complications