Study of Intratumoral (IT) Ulevostinag (MK-1454) in Combination With Intravenous (IV) Pembrolizumab (MK-3475) Compared to IV Pembrolizumab Alone as the First Line Treatment of Metastatic or Unresectable, Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC) (MK-1454-002)

Inclusion Criteria:

• Has histologically or cytologically confirmed diagnosis of metastatic orunresectable, recurrent head and neck squamous cell carcinoma (HNSCC) that isconsidered incurable by local therapies

• Has not had prior systemic therapy administered in the recurrent or metastaticsetting

• Has tumor PD-L1 expression of CPS ≥1. Tumor tissue must be provided for PD-L1biomarker analysis

• Has measurable disease per RECIST 1.1, as assessed by BICR

• Has at least 1 measurable lesion which is amenable to injection

• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

• Demonstrates adequate organ function within 7 days prior to treatment initiation

• Male participants of reproductive potential must agree to refrain from donatingsperm and use a male condom plus partner use of an additional contraceptive methodduring sexual contact with females of childbearing potential during the interventionperiod with ulevostinag and for at least 120 days after the last dose of ulevostinag

• Female participants of childbearing potential who are not pregnant or breastfeedingmust be willing to use a highly effective method of birth control or be surgicallysterile or abstain from heterosexual activity during the intervention period and forat least 120 days after the last dose of study intervention, and agree not to donateeggs (ova, oocytes) to others or freeze/store for personal use

• Human immunodeficiency virus (HIV)-infected participants must meet these additionalcriteria:

1. Has HIV-1 infection documented by using any licensed rapid HIV test or HIVenzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior tostudy entry (Day 1)

2. Has well-controlled HIV on anti-retroviral therapy (ART)

Exclusion Criteria:

• Has disease that is suitable for local therapy administered with curative intent

• Has progressive disease (PD) within 6 months of completion of curatively intendedsystemic treatment for locoregionally advanced HNSCC

• Has had chemotherapy or biological cancer therapy in the recurrent or metastaticsetting for the treatment of HNSCC

• Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior torandomization or participant has not fully recovered from adverse events (AEs) dueto a previously administered treatment

• Is expected to require any other form of antineoplastic therapy while on study

• Has a history of a second malignancy, unless potentially curative treatment has beencompleted, with no evidence of malignancy for at least 2 years

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

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

• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or anyother form of immunosuppressive therapy within 7 days prior to the first dose ofstudy treatment

• Has had an allogenic tissue/solid organ transplant

• Has a history of vasculitis

• Has a history of interstitial lung disease

• Has an active infection requiring systemic therapy

• Has a known history of active tuberculosis (TB; Bacillus tuberculosis)

• Has a history of (non-infectious) pneumonitis that required steroids or currentpneumonitis

• Has had a severe hypersensitivity reaction to treatment a monoclonalantibody/components of the study treatment

• Has known Hepatitis B virus or Hepatitis C virus infections

• Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1),anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed celldeath-ligand 2 (anti-PD-L2) agent or if the participant has previously participatedin Merck Sharp & Dohme (MSD) MK-3475 clinical trials

• HIV infected participant who has had an HIV-related opportunistic infection within 6months

• HIV infected participants who have a history of Kaposi's sarcoma and/or MulticentricCastleman's Disease

• Is pregnant, breastfeeding, or expecting to conceive or father children within theprojected duration of the study, starting with the screening visit through 120 daysafter the last dose of study treatment

• Has not fully recovered from any effects of major surgery without significantdetectable infection

• Has a history of re-irradiation for HNSCC at the projected injection site in thehead and neck

• Has received a live-virus vaccine within 30 days of planned study treatment start

• Has been treated with a stimulator of interferon genes (STING) agonist (e.g.ulevostinag, ADU-S100)

• Is currently participating and receiving study therapy or has participated in astudy of an investigational agent and received study therapy, or used aninvestigational device, any of which occurred within 4 weeks of the first dose ofstudy treatment