A Clinical Study of Intismeran Autogene (V940) and Pembrolizumab (MK-3475) in People With Melanoma (V940-012/INTerpath-012)

Inclusion Criteria

• Inclusion Criteria: The main inclusion criteria include but are not limited to the following: - Has unresectable and histologically confirmed Stage III or IV cutaneous melanoma per American Joint Committee on Cancer (AJCC) Eighth Edition guidelines. - Has been untreated for melanoma except if participant received prior adjuvant or neoadjuvant therapy with targeted therapy or immunotherapy (such as anti-cytotoxic T-lymphocyte-associated protein [CTLA-4], anti-programmed cell death 1 protein [PD-1] therapy or interferon), and only if relapse did not occur within 12 months after treatment discontinuation. - Have documentation of serine/threonine-protein kinase B-raf (BRAF) V600-activating mutation status or had BRAF V600 mutation testing per local institutional standards during the screening period (participants with BRAF mutation positive melanoma as well as BRAF wild-type or unknown are eligible). - Have the presence of at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by the local site investigator/radiology assessment. - Provides tumor tissue (preferably from a metastatic site and, if not available, from the primary tumor) that is suitable for next generation sequencing and biomarker analysis as required for this study. - Participants with human immunodeficiency virus (HIV) must have well controlled HIV on antiretroviral 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. Exclusion Criteria: The main exclusion criteria include but are not limited to the following: - Has clinically significant heart failure, defined as New York Heart Association class III or IV, within the past 6 months, unless the disease is well controlled in the opinion of the investigator. - HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease. - Has ocular or mucosal melanoma. - 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 blood sample for V940 generation). - Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, lymphocyte activation gene 3 [LAG-3], tumor necrosis factor receptors [OX-40 or CD137]), with some exceptions. - Received prior systemic anticancer therapy for melanoma before randomization, with some exceptions. - Received prior radiotherapy within 2 weeks of start of study intervention or has ongoing radiation related toxicities. - Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. - Received prior treatment with another universal or personalized cancer vaccine.