A Clinical Study of Intismeran Autogene (V940) Plus Pembrolizumab in People With High-Risk Melanoma (V940-001)

The purpose of this study is to learn if intismeran autogene which is an individualized neoantigen therapy (INT; formerly, called messenger ribonucleic acid \[mRNA\]-4157) with pembrolizumab (MK-3475) is safe and prevents cancer from returning in people with high-risk melanoma. Researchers want to know if intismeran autogene with pembrolizumab is better than receiving pembrolizumab alone at preventing the cancer from returning.

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has surgically resected and histologically/pathologically confirmed diagnosis of Stage IIB or IIC, III, or IV cutaneous melanoma * Has not received any prior systemic therapy for their melanoma beyond surgical resection * No more than 13 weeks have passed between final surgical resection that rendered the participant disease-free and the first dose of pembrolizumab * Is disease free at the time of providing documented consent for the study * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy (ART) Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has ocular or mucosal melanoma * Has cancer that has spread to other parts of the body and cannot be removed with surgery * Has heart failure within the past 6 months * Has received prior cancer therapy or another cancer vaccine * Has another known cancer that that has spread to other parts of the body or has required treatment within the past 3 years * Has severe reaction to study medications or any of their substance used to prepare a drug * Have not recovered from major surgery or have ongoing surgical complications