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

Inclusion Criteria:

Inclusion Criteria include, but are not limited to:

• Has a histologically or cytologically confirmed diagnosis of squamous non-small celllung 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 thediagnosis 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 withhormone replacement or participants who have ≤Grade 2 neuropathy are eligible

• Human immunodeficiency virus (HIV)-infected participants must have well controlledHIV on antiretroviral therapy (ART)

• Hepatitis B surface antigen (HBsAg) positive participants are eligible if they havereceived hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and haveundetectable HBV viral load prior to randomization

• Participants with history of hepatitis C virus (HCV) infection are eligible if HCVviral load is undetectable. NOTE: Participants must have completed curativeantiviral therapy at least 4 weeks prior to randomization

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1assessed 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'sDisease

• Has received prior treatment with a cancer vaccine, including another personalizedcancer 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 deathligand 2 (anti-PD-L2) agent, or with an agent directed to another stimulatory orcoinhibitory 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 NSCLCis allowed as long as therapy was completed at least 12 months before diagnosis ofmetastatic NSCLC

• Has received prior radiotherapy within 2 weeks of start of study intervention, orhas radiation-related toxicities, requiring corticosteroids

• Has received radiation therapy to the lung that is >30 gray within 6 months of startof study intervention

• Has received a live or live-attenuated vaccine within 30 days before the first doseof study intervention. Administration of killed vaccines is allowed

• Has received an investigational agent or has used an investigational device within 4weeks 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 ofimmunosuppressive therapy within 7 days prior to the first dose of studyintervention

• Has known additional malignancy that is progressing or has required active treatmentwithin the past 3 years

• Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis

• Has severe hypersensitivity (≥Grade 3) to V940, pembrolizumab, or any of theprotocol allowed chemotherapy agents and/or any of their excipients

• Has active autoimmune disease that has required systemic treatment in the past 2years

• Has a history of (noninfectious) pneumonitis/interstitial lung disease that requiredsteroids 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 surgicalcomplications