INTerpath-007: This study is recruiting people who locally advanced cutaneous squamous cell carcinoma that is able to be removed through surgery, and will evaluate the effectiveness of a medicine called V940 plus immunotherapy when given before and after surgeryA Phase 2/3, Adaptive, Randomized, Open-label, Clinical Study to Evaluate Neoadjuvant and Adjuvant V940 (mRNA-4157) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care, and Pembrolizumab Monotherapy in Participants With Resectable Locally Advanced Cutaneous Squamous Cell Carcinoma (LA cSCC)

Exclusion

• Has any other histologic type of skin cancer other than invasive cSCC as well as mixed histology, eg, basal cell carcinoma that has not been definitively treated with surgery or radiation, Bowen's disease, Merkel cell carcinoma (MCC), or melanoma
• Has distant metastatic disease (M1), visceral and/or distant nodal
• Has received prior therapy with an anti-programmed cell death receptor 1 (anti-PD-1), anti-programmed cell death receptor ligand 1 (anti-PD-L1), or anti-programmed cell death receptor ligand 2 (anti-PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte associated protein 4 (CTLA-4), OX-40, CD137)
• Has received prior systemic anticancer therapy including investigational agents for cSCC before randomization
• Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 2 weeks of the screening blood sample (including the NGS blood sample)
• Has received prior treatment with another cancer vaccine
• Has received prior radiotherapy to the index lesion (in-field lesion). Must have recovered from all radiation-related toxicities prior to randomization and not have had radiation pneumonitis
• 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 the first dose of study medication
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
• History of chronic lymphocytic leukemia (CLL)
• History of central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has severe hypersensitivity (≥Grade 3) to either V940 or pembrolizumab and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Has HIV with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Has concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection
• Has had a myocardial infarction within 6 months of randomization
• Has a history of allogeneic tissue/solid organ transplant
• Has not adequately recovered from major surgery or have ongoing surgical complications